No Improvement in Local Tumor Response by adding Oxaliplatin to Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer

A large, multicenter Italian study has found that adding oxaliplatin (Eloxatin, Sanofi-Aventis) to standard preoperative radiochemotherapy in patients with locally advanced rectal cancer does not improve tumor shrinkage.

However, preliminary and exploratory data from the study, presented on Saturday, May 30, 2009 by Carlo Aschele, MD, PhD, E.O. Ospedali Galliera, (Mura delle Cappuccine, 1416128 Genova (Ligurie), Italy, Phone +39 010 5 6321) during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held from May 27 – June 2, 2009 in Orlando, Florida, suggest that it may reduce the number of distant metastases.

Chemotherapy and radiation are often administered before surgery for rectal cancer to shrink the tumor and make it easier to remove. Previous results from this study showed that although adding oxaliplatin to standard chemotherapy increased some side effects, especially diarrhea, it did not affect the ability to deliver the full course of radiation therapy or to perform surgery. Oxaliplatin has been found effective and is commonly used in patients with more advanced colon and rectal cancer.

In this phase III trial, 747 patients with locally advanced rectal cancer were randomized to receive standard preoperative chemoradiotherapy or the standard plus oxaliplatin. Researchers found no significant difference between the two groups in terms of tumor reduction: 16 percent of patients in both groups had no tumor present at the time of surgery, and 29 percent in the oxaliplatin group had mildly invasive tumors (T1 or T2) without nodal involvement, compared with 30 percent in the control group. There was also no significant difference in the number of patients who had cancer in the lymph nodes (27 percent in the oxaliplatin group versus 25 percent in the control group). Consistently, the proportions of patients who could have conservative surgery were similar between the two arms.

In an unplanned analysis, when looking at intra-abdominal disease spread at the time of surgical removal of the primary tumor, only 0.5 percent of patients in the oxaliplatin group (2 patients) had distant metastases, versus 3 percent in the control group (11 patients), a difference that was statistically significant.

“Although adding oxaliplatin to the current standard of care did not improve tumor response rates, we found this course of treatment was associated with a reduced number of early distant metastases in the abdomen in a very small number of patients,” said Carlo Aschele, MD, PhD, attending physician and lead clinician in Colorectal/Gastrointestinal Cancer in the Department of Medical Oncology and Cancer Prevention at E.O. Ospedali Galliera in Genoa, Italy, and the study’s first author.

“Although the numbers are very small and the analysis of distant metastases was unplanned and exploratory, the difference is significant and indicates that the lack of an effect on local tumor shrinkage does not necessarily imply a lack of effect on micrometastases at distant sites. Longer follow-up is necessary to assess whether treatment with oxaliplatin will have an effect on recurrence rates or survival.”

Note: This article contains updated data not published in the original ASCO 2009 abstract

For more information:

• Aschele C, Pinto C, Cordio S, Rosati G, Tagliagambe A, Artale S, Rosetti P, Lonardi S, Boni L, Cionini L. Preoperative fluorouracil (FU)-based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: Pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)-01 randomized phase III trial. Abstract: CRA4008
• American Society of Clinical Oncology (ASCO)

Standard of Care for Anal Cancer Should Not Be Changed

Findings from the largest trial ever conducted for anal cancer have shown that the current standard of care, using a novel, continuous radiation therapy delivery program combined with 5-fluorouracil (5-FU) , (a drug commonly used to treat many types of cancer including, breast, head and neck, anal, stomach, colon and some skin cancers), and mitomycin-C (a chemotherapy drug mainly used to treat bladder and rectal cancers, but also sometimes pancreatic, lung and breast cancers), results in the best outcomes so far reported for patients with anal cancer, and that cisplatin chemotherapy (a drug approved to be used together with other drugs to treat many different cancers), is not superior to mitomycin-C.

The study, presented on Saturday, May 30, 2009 by Roger James, MD, Maidstone Hospital, Kent, UK, during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held from May 27 – June 2, 2009 in Orlando, Florida, also showed no evidence of a benefit of adding maintenance chemotherapy to the standard of care.

Anal cancer is rare, with about 5,000 patients diagnosed in the United States each year. In the United Kingdom about 850 people are diagnosed with this disease each year. It is slightly more common in women than men, with rates increasing in women over the past 10 years.

Unlike colorectal cancer, the majority of patients with anal cancer do not need surgery, largely because the tumors are the squamous cell type, which are very responsive to chemotherapy and radiation. Cisplatin is commonly used for other squamous cell cancers, but it is less convenient to deliver and is known to have different toxicities from mitomycin-C, such as neurological and renal side effects and hearing loss.

The current study, called ACT II, conducted by the National Cancer Research Institute in the United Kingdom, and funded by Cancer Research UK, randomized 940 patients to receive radiation therapy given at the same time as 5-FU with either mitomycin-C or cisplatin. Patients were also randomized to receive follow-up maintenance therapy with cisplatin and 5-FU after chemoradiation or no maintenance therapy.

After a median follow-up of three years, the investigators found no significant difference in outcome in the two randomized comparisons:

• The complete response rate at 6 months (the number of patients who had all signs of their cancer disappear) was 94 percent in the mitomycin-C group compared with 95 percent in the cisplatin group.
• Recurrence-free survival at 3 years (the number of patients whose tumors did not return) was 75 percent both in patients who got maintenance therapy and in those who did not.
• Overall survival at 3 years was 85 percent in patients who received maintenance therapy and 84 percent in those who did not.

“These findings are good news in spite of the lack of evidence for an improvement in giving either cisplatin or maintenance therapy, since the standard chemoradiation schedule given in this trial was highly effective,” said Roger James, MD, FRCP, FRCR, a radiation oncologist from Maidstone Hospital, Kent, United Kingdom, and the study’s lead author. “Although this trial did not show an improvement from adding maintenance therapy, some form of additional treatment will be the subject of future studies, to determine whether some subset of patients might benefit from it.”

For more information:

• The National Cancer Research Institute (NCRI)
• Cancer Research UK
• Anal Cancer trials (UK)
• Glynne-Jones R, Mawdsley S, Anal Cancer: The End of the Road for Neoadjuvant Chemoradiotherapy? Journal of Clinical Oncology (JCO), Vol 26, No 22 (August 1), 2008: pp. 3669-3671

2009 ASCO Annual Meeting Abstracts:

• James R, Wan S, Glynne-Jones R, Sebag-Montefiore D, Kadalayil L, Northover J, Cunningham D, Meadows M, Ledermann J, National Cancer Research Institute (NCRI) ACT II Trial Management Group. A randomised trial of chemoradiation using mitomycin or cisplatin, with or without maintenance cisplatin/5FU in squamous cell carcinoma of the anus (ACT II) LBA4009

Illustration courtesy of the American Society of Clinical Oncology.

Surgical Removal of the Primary Tumor Not Immediately Needed in Patients with Metastatic Colorectal Cancer

New research shows that patients who are newly diagnosed with metastatic, surgically incurable, colorectal cancer (mCRC) do not need immediate surgery to remove their primary tumor unless the tumor is causing complications.

Surgical removal of the primary tumor at the time of diagnosis was once standard practice and is still common in patients with metastatic colorectal cancer. Because cancer has already spread to other parts of the body by this stage, the purpose of this surgery is not to extend survival, but to prevent future complications, such as intestinal blockage, perforation of the bowel, and severe bleeding. However, over the past decade several new effective chemotherapy drugs for colorectal cancer have been introduced and until now there has been little data to assess whether this pre-emptive surgery is still warranted.

The research will be presented on Monday, June 1, by Philip B. Paty, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held from May 27 – June 2, 2009 in Orlando, Florida.

Incidence of metastatic Colorectal Cancer (mCRC)
According to GLOBOCAN 2002, a cancer incidence database produced by the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO), the worldwide incidence of colorectal cancer is approximately one million cases per year. The National Cancer Institute (NCI) reports that approximately 50 percent of patients diagnosed with colorectal cancer will suffer from advanced disease that has metastasized to other parts of the body, most commonly to the liver.

Uncertain benefit
The researchers rationale is that in the absence of symptoms (bleeding, perforation, obstruction) or resectable metastatic disease, primary tumor resection in patients who present with synchronous metastatic colorectal cancer (mCRC) is of uncertain benefit.

The purpose of their study was to describe the frequency of intervention necessary to palliate the intact primary tumor in patients who present with synchronous stage IV CRC and receive up-front modern combination chemotherapy without prophylactic surgery.

“In this era of modern chemotherapy, routine surgery to remove the primary tumor in patients with unresectable metastases is no longer supported by the data,” explained Philip Paty, MD, an attending surgeon and vice chairman of clinical research at Memorial Sloan-Kettering Cancer Center (MSKCC) and the study’s senior author. “In addition to being an unnecessary procedure that carries its own risks of morbidity and mortality, surgery delays the start of chemotherapy for several weeks, and in some cases may make the patient less fit for and less tolerant of chemotherapy. Unless there is an immediate need for surgery, patients should begin chemotherapy first.”

FOLFOX, IFL and FOLFIRI
This retrospective study identified 233 consecutive patients who presented with metastatic colorectal cancer between 2000 and 2006, and were treated with chemotherapy at MSKCC, but had no serious symptoms to prompt immediate surgery. The patients received one of three triple-drug chemotherapy combinations as their initial treatment (the regimens known as FOLFOX, IFL, and FOLFIRI).

Some were also treated with the targeted therapy bevacizumab (Avastin, Roche).

Investigators determined that 217 (93%) patients never developed complications that required removal of their tumor. For the 16 patients (7%) who did eventually need surgery, the vast majority (14/16) had successful operations.

10 patients (4%) required nonoperative intervention (stent or radiotherapy), whereas 213 (89%) never required any direct symptomatic management for their intact primary. Of those, 47 (20%) ultimately underwent elective colon resection at the time of metastasectomy and 8 (3%) during laparotomy for hepatic artery infusion pump placement. Neither use of bevacizumab, location of the primary tumor in the rectum, or metastatic disease burden was associated with increased intervention rate. In addition, when included as a time-varying covariate in a Cox regression model, the need for emergent intervention did not correlate with overall survival.

Most patients with synchronous stage IV CRC who receive up-front modern combination chemotherapy never required palliative surgery for their intact primary. The data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease.

Overall, the researchers concluded that the mortality attributable to surgery was very low (0.8 percent), suggesting that this approach, by avoiding unnecessary surgery, improves the overall safety of treatment.

For more information:

• American Society for Clinical Oncology (ASCO)
• Poultsides GA , Servais EL, Saltz LB, Patil S, Kemeny NE, Guillem JG, Weiser M, Temple LK, Wong W, Paty PB. Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial Treatment. CRA4030

PubMed abstracts:

• Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. 2009 Apr 30. [Epub ahead of print].
• Dy GK, Hobday TJ, Nelson G, Windschitl HE, O'Connell MJ, et al. Long-term survivors of metastatic colorectal cancer treated with systemic chemotherapy alone: a north central cancer treatment group review of 3811 patients, n0144. Clin Colorectal Cancer. 2009 Mar;8(2):88-93.
• Tamandl D, Gruenberger B, Herberger B, Kaczirek K, Gruenberger T. Surgery after neoadjuvant chemotherapy for colorectal liver metastases is safe and feasible in elderly patients. J Surg Oncol. 2009 Feb 20. [Epub ahead of print]
• Cao Y, Liao C, Tan A, Liu L, Mo Z, Gao F. Capecitabine plus oxaliplatin versu fluorouracil plus oxaliplatin as first line treatment for metastatic colorectal caner - meta-analysis of six randomized trials. Colorectal Dis. 2009 Feb 7. [Epub ahead of print]

Other ASCO 2009 abstracts:

• A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: Results of NSABP Protocol C-08.
  Meeting:2009 ASCO Annual Meeting Abstract No: LBA4 First Author: N. Wolmark Category: Gastrointestinal (Colorectal) Cancer - Colorectal Cancer (including liver metastases)
• A quantitative multigene RT-PCR assay for prediction of recurrence in stage II colon cancer: Selection of the genes in four large studies and results of the independent, prospectively designed QUASAR validation study.
  Meeting:2009 ASCO Annual Meeting Abstract No: 4000 First Author: D. KerrCategory:Gastrointestinal (Colorectal) Cancer - Colorectal Cancer (including liver metastases)
• Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial).
  Meeting:2009 ASCO Annual Meeting Abstract No: 4001 First Author: S. TejparCategory:Gastrointestinal (Colorectal) Cancer - Colorectal Cancer (including liver metastases)

Illustration courtesy of the American Society of Clinical Oncology.

Bevacizumab study does not meet primary endpoint, but results suggest future trials may hold promise for early-stage colon cancer treatment

Adding bevacizumab to standard adjuvant chemotherapy does not improve disease-free survival for early-stage colon cancer. This is the primary conclusion from the complete results from the first, randomized phase III trial of bevacizumab (Avastin, Roche) in early-stage colon cancer, known as NSABP C-08, conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and sponsored by the National Cancer Institute (NCI) under a Cooperative Research and Development Agreement between Genentech and NCI, and will be presented on Sunday, May 31, during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held from May 27 – June 2, 2009 in Orlando, Florida.

NSABP C-08 was the first study to report results on the use of bevacizumab as an adjuvant treatment. Bevacizumab targets the vascular endothelial growth factor (VEGF) receptor, a key driver of tumor angiogenesis – an essential process in the development and maintenance of blood vessels which is required for a tumor to grow and to spread (metastasize) to other parts of the body.

The results of the NSABP C-08 trial have found that adding bevacizumab to standard adjuvant chemotherapy did not improve disease-free survival (the time that patients are free of tumor recurrence) in early-stage colon cancer

The current study enrolled 2,710 patients who were randomized to receive six months of standard adjuvant chemotherapy or six months of adjuvant chemotherapy combined with bevacizumab plus an additional six months of bevacizumab after the chemotherapy had ended.

All patients in the study had stage II or stage III disease and first had surgery to remove their tumors. After a median follow-up of three years, the investigators found that 77.4 percent of patients in the experimental group (bevacizumab) were alive and free of disease, compared with 75.5 percent of patients in the control group, a difference that was not statistically significant. There were no unexpected side effects in either arm and the toxicities from bevacizumab were well tolerated.

“One interesting effect was that during the year that patients were receiving bevacizumab we saw a benefit in disease-free survival (DFS) that subsequently diminished when follow-up was completed,” said Norman Wolmark, MD, chairman of the Department of Human Oncology at Allegheny General Hospital and the study’s lead author. Patients receiving bevacizumab treatment had a 40 percent lower risk of cancer returning, however, this initial improvement over chemotherapy alone gradually diminished over time.

Commenting on the trial, Walmark continued “Our overall conclusion is that bevacizumab was not effective as an adjuvant treatment for early-stage colon cancer, but the transient benefit we saw in patients who received bevacizumab illustrates that we have more to learn about how this reagent works, and we need to design more clinical trials to determine how it can be used most effectively.”

No new safety signals for bevacizumab were observed in the study and careful review of the data did not provide evidence that cancer returns faster or more aggressively after bevacizumab therapy was stopped.

“These results are encouraging and suggest that Avastin may have an important role in early cancer treatment. We are committed to the ongoing program of Avastin in early-stage cancers and believe that these results could help us optimize the use of Avastin for the benefit of patients,’’ noted William M. Burns, CEO of the pharmaceutical division of Roche, a leader in research-focused healthcare.

Study Results
The NSABP C-08, a two-arm randomized prospective multi-center Phase III study evaluated the use of bevacizumab plus chemotherapy (mFolfox6 + bevacizumab/mFF6+B) for the treatment of Stage II or III adenocarcinoma immediately following surgery (adjuvant therapy) compared to chemotherapy alone (mFolfox6/mFF6). The study showed the addition of one year of bevacizumab to chemotherapy did not result in a statistically significant improvement in overall disease-free survival (DFS). However, during the year of bevacizumab treatment there was an early and significant improvement in disease-free survival that diminished over the course of the study.

Disease-Free Survival was measured from the date of randomization to the date of any type of cancer recurrence or death from any cause. Patients enrolled in the study were randomized after surgery to receive either FOLFOX chemotherapy alone for six months or FOLFOX in combination with bevacizumab (intravenously every two weeks) for six months, followed by an additional six months of bevacizumab monotherapy. Patients continue to be followed for overall survival, a secondary endpoint of the study.

Overall in the study, there was 12 percent improvement in DFS that was not statistically significant (hazard ratio=0.89, p=0.15; risk reduction 11 percent). In the first year of the study, while patients received bevacizumab in addition to a standard six-months of adjuvant chemotherapy, disease-free survival improved by 67 percent compared to chemotherapy alone (hazard ratio=0.60; risk reduction of 40 percent). However, this early improvement in DFS began to diminish after the first year, and overall DFS was not improved.

NSABP C-08 included a comprehensive safety analysis that showed no new or unexpected safety events related to bevacizumab in the study. Specific severe (Grade 3 or greater) adverse events (AEs) that occurred with increased frequency in patients who received bevacizumab versus chemotherapy alone were: hypertension (12 percent vs. 1.8 percent), pain (11.1 percent vs. 6.3 percent), proteinuria (2.7 percent vs. 0.8 percent) and wound-healing complications (1.7 percent vs. 0.3 percent).

Other trials and standard of care
Bevacizumab is currently approved for metastatic colorectal, breast, and lung cancers and other trials are ongoing to evaluate it as an adjuvant treatment for a variety of solid tumors. Therapy with bevacizumab is the standard of care in advanced colon cancer treatment which will be further confirmed throughout the ASCO meeting with 53 efficacy and safety data presentations including more than 6,000 patients.

In addition to early-stage colon cancer, bevacizumab is being studied as an adjuvant treatment in other early-stage diseases: HER2-negative breast cancer, HER2-positive breast cancer, and non-squamous, non-small cell lung cancer. Approximately 26,000 people are expected to participate in bevacizumab based adjuvant studies, making the bevacizumab development program one of the most comprehensive undertakings in cancer research since chemotherapy. The Avastin (bevacizumab) development program includes more than 450 clinical trials worldwide in approximately 30 different tumor types.

More than 500,000 patients have been treated with bevacizumab so far. A comprehensive clinical program with more than 450 clinical trials is investigating the use of bevacizumab in various tumor types (including colorectal, breast, lung, brain, gastric, ovarian, prostate and others) and different settings (advanced or early stage disease).

Mode of Action
The precise mode of action of bevacizumab helps control tumor growth and metastases with only a limited impact on side effects of chemotherapy.

The drug has proven survival benefits across multiple tumor types and is approved in Europe for the treatment of the advanced stages of four common types of cancer, including colorectal cancer, breast cancer, lung cancer and kidney cancer. These types of cancer collectively cause nearly 3 million deaths each year in the US alone.

In the US, bevacizumab was the first anti-angiogenesis therapy approved by the FDA and is now approved for the treatment of four tumor types: breast, colorectal, glioblastoma, and non-small cell lung cancer (NSCLC).

For further information:

• American Society for Clinical Oncology
• Wolmark, G. Yothers, M. J. O’Connell, S. Sharif, J. N. et al. A phase III trial comparing mFolfox6 to mFolfox6 + bevacizumab in stage II or III carcinoma of the colon: Results of NSABP Protocol C-08 N. Plenary presentation, Sunday, May 31, 3:15 PM EDT, Level 2, West Hall D2. Plenary Session, Lead Author: Norman Wolmark, MD, Allegheny General Hospital Pittsburgh, Pa. Abstract No# LBA4

Other, related, abstracts

• A quantitative multigene RT-PCR assay for prediction of recurrence in stage II colon cancer: Selection of the genes in four large studies and results of the independent, prospectively designed QUASAR validation study.
  Meeting:2009 ASCO Annual Meeting Abstract No: 4000 First Author: D. KerrCategory:Gastrointestinal (Colorectal) Cancer - Colorectal Cancer (including liver metastases)
• Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial).
  Meeting:2009 ASCO Annual Meeting Abstract No: 4001 First Author: S. TejparCategory:Gastrointestinal (Colorectal) Cancer - Colorectal Cancer (including liver metastases)
• Stage-specific prognostic value of molecular markers in colon cancer: Results of the translational study on the PETACC 3-EORTC 40993-SAKK 60-00 trial.
  Meeting:2009 ASCO Annual Meeting Abstract No: 4002 First Author: A. D. RothCategory:Gastrointestinal (Colorectal) Cancer - Colorectal Cancer (including liver metastases)

Folfox Background information:

• Wikipedia (Definition)
• Cancer Research UK
• NCI – National cancer Institute

Colorectal Cancer:

• Medical Oncology (at Boomja.com)
• Goldberg RM, Therapy for Metastatic Colorectal Cancer The Oncologist Vol. 11, No. 9, 981-987, October 2006

Pharmaceutical information:

• EMEA - European Public Assessment Report (bevacizumab)
• Highlights of Prescribing Information USA (bevacizumab)
  

New studies answer key questions about the treatment of gastrointestinal cancers

Findings from a number of large clinical trials of new treatment regimens for gastrointestinal cancers were released today at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), being held in Orlando, May 29 - June 2, 2009 and will be highlighted in Onco’Zine – The international Cancer Blog.

“The studies presented today answer many important questions about the best care for people with gastrointestinal cancers,” said Nicholas Petrelli, MD, medical director of the Helen F. Graham Cancer Center in Wilmington, Delaware. “These large, conclusive trials tell us what works, and importantly, tell us what doesn’t work. Some settle long-time debates in the field, others demonstrate that the current standard of care is actually superior to experimental treatments, and others will allow patients to avoid unnecessary side effects or surgery.”

The results presented include:

• First-ever data on bevacizumab as adjuvant therapy finds no benefit in colon cancer: A phase III trial finds that adding the targeted therapy bevacizumab (Avastin, Roche), to standard adjuvant chemotherapy did not improve disease free survival for patients with locally advanced colon cancer.
• Surgery unnecessary for majority of patients with advanced colorectal cancer: Most patients with metastatic colorectal cancer can safely avoid surgery on their primary tumors.
• A trial compares common adjuvant treatments for pancreatic cancer: A phase III trial comparing the adjuvant treatments most commonly used for pancreatic cancer in the United States and Europe, gemcitabine (Gemzar, Eli Lilly and Company) and 5-FU/FA, respectively, found that there is no difference in survival between the two regimens, though gemcitabine was associated with fewer side effects.
• The largest study to date on anal cancer supports the current standard: A phase III study finds that the current standard of care for anal cancer should not be changed, and that ongoing maintenance therapy after initial treatment is not effective.
• Oxaliplatin does not improve outcomes for rectal cancer: Adding oxaliplatin (Eloxatin, Sanofi-Aventis) to standard treatment in patients with locally advanced rectal cancer does not improve tumor response. However, a preliminary analysis seems to suggests that the treatment may reduce distant metastases.

For more information:

• American Society of Clinical Oncology
• 2009 ASCO annual meeting abstracts

Reference:

• Medical-Oncology (at Boomja.com)

An Unusual Request: Help the Melanoma Research Foundation

The Melanoma Research Foundation (MRF) is working with a U.S. women's health magazine that’s writing an article highlighting that melanomas can appear in areas that don't get a lot of UV exposure. For this article they are looking looking for a young woman who has (or had) melanoma to profile in the story.

Specifically, the magazine is looking for a woman meeting the following caracteristics:

• In her 20’s, 30’s or 40's
• Lives in the United States
• Recently diagnosis with stage III or IV melanoma (within the past few years)
• The melanoma was found in an area that doesn’t get sun exposure or very surprising place such as the groin, fingers, toes, nail beds, palms, the soles of feet or eyes.
• Did not tan
• Did not have any other health issue when she was diagnosed (otherwise healthy and in shape)
• Is available for a phone interview this week.

If this describes you or one of your patients or someone you know, please contact the Melanoma Research Foundation. The link takes give access to a form you or your patient should complete. The Melanoma Research Foundation will contact the you or your patient and the writer to schedule phone interview.

For more information:

• Help the Melanoma Research Foundation

New diagnostic procedures: a new, quick test for prostate cancer

Prostate cancer is the most common cancer diagnosed in men in the UK and many other developed countries, including the United States. In the UK 35,000 men are diagnosed each year with prostate cancer. To emphasis the gravity of the disease, one man dies every hour of prostate cancer in the UK. African Caribbean men are three times more likely to develop prostate cancer than Caucasian men. In the United States, the estimated number of new cases prostate cancer is more than 192,000 with 27,000 deaths.

A new, fast, diagnostic procedure
Researchers have developed the test by using light energy to measure the level of citrate in fluid samples from the prostate gland. The technique could provide the basis of a rapid means of detecting prostate cancer in the future. Almost a quarter of male cancers in the UK are diagnosed as prostate cancer and more than 10,000 men die from the disease each year.

Scientists, led by Prof David Parker from Durham University’s Chemistry Department, have worked with experts from the University of Maryland, USA to develop the technique that measures the wavelength of light as it is shone through diluted samples of body fluids.

The research team, funded by the North East Proof of Concept Fund and the EPSRC, believe that the technique which can measure, with speed and accuracy, how citrate levels fall in the prostate gland as cancer develops, could also find use for the diagnosis of other medical conditions, associated with poor kidney function.

Prof Parker said: “Citrate provides a significant biomarker for disease that may provide a reliable method for screening and detecting prostate cancer, and for the monitoring of people with the disease. This technique could form the basis of a simple screening procedure for prostate cancer that could be used in outpatient departments at local hospitals.”

His team have shone light into over 100 different chemical structures to see how they function and respond to the presence of certain important bioactive species. They have looked particularly closely at how citrate and lactate bind to luminescent structures within fluids. Citrate and lactate are vital for our bodies’ metabolism for normal function. Citrate provides energy for cells and the amount found in the prostate varies considerably due to an enzyme called m-aconitase which transforms it. This enzyme is very sensitive to zinc and, in prostate cancer sufferers, zinc levels are depressed and the enzyme switches on again.

Prof Leslie Costello from the University of Maryland said: “Citrate is formed in cell metabolism processes which alter as cancers grow. The analysis of the citrate concentration of prostatic fluid can provide an accurate way to screen and diagnose prostate cancer. Since citrate concentrations decrease markedly early in malignancy, this technique makes it possible to analyse what’s happening quickly in the early and treatable stage of prostate cancer. It shows much promise as a clinical tool.”

The new test requires only a microlitre of fluid and the sample can be easily measured in an optical instrument. Using samples from male volunteers, the researchers have developed a portable instrument that can give results in 3 minutes.

The team’s challenge has been how to accurately measure changes in the amount of citrate or lactate in fluid samples using the technique. The early results are promising and the team intends to look at the analysis of other body fluids. A possible way forward is to examine the citrate levels in seminal fluid samples, which are made up of 50% prostate fluid.

Technology Transfer
The University has launched a spin-out company called FScan Ltd to develop the technique and to seek commercial backing. The team has looked at 20 samples so far and verified the analysis in every case. The next stage is to work with a local hospital and examine samples from 200 volunteers to see whether the first Durham results correlate.

Prof Parker says: “It’s been a complex process to develop the technique but we’re very optimistic about it. Ultimately, this could provide an accurate method of screening for prostate cancer in men that could be carried out in 3-minutes once a biopsy has been obtained from the patient at a hospital outpatient department.”

The Prostate Cancer Charity believes that this new, three minute test could effectively help to diagnose prostate cancer.

The discovery follows the invention in 2006 by Durham University Professor Douglas Newton of a Urine Flow Meter. The UFlow Meter helps men to assess if they have a restricted rate of urine flow - one of the warning signs of prostate problems.

The establishment of FScan Ltd is part of the University’s aim to enhance the exploitation of the Intellectual Property generated by high quality research activities.

Tim Hammond, Head of Technology Transfer at Durham University, said: '”We quickly realised the potential of this research and have worked closely with Professor Parker and his team to secure initial proof of concept funding through NorthStar Equity Investors and the North East Proof of Concept Fund and to establish FScan Limited as the vehicle to validate and commercialise the technology.”

John Neate, Chief Executive of The Prostate Cancer Charity, an organization striving for a world where lives are no longer limited by prostate cancer,explains: “This is early stage research, with the citrate levels of only 20 samples being tested. The results of a biopsy take around two weeks to come back to a patient and the main benefit of this new potential test would be one of speed. If the findings of further research in a large group of men remain consistent with these early results, the test could add something beneficial to the diagnostic tools currently available. Men could have a clearer idea of whether they have the disease, before the biopsy results confirm this. The full biopsy results would still be necessary, however, to confirm whether a man has an aggressive or non-aggressive form of the disease."

“The benefit of the test to men living with non-aggressive forms of prostate cancer, who are being treated with active surveillance, is less clear. This new test, which involves the insertion of a needle into the prostate under local anaesthetic, is an invasive procedure when compared to the current practice of monitoring the progression of the disease using the PSA blood test. The researchers hope to able to refine the test by using samples of seminal fluid which may be easier to obtain. If this was the case, it would be easier to see how this test could take a useful place in clinical practice."

“The acceptability of the test as a broader screening tool is problematic, given its invasive nature.”

Process for testing
1. Sample of prostatic fluid taken from patient in hospital using local anaesthetic
2. 200 fold dilution of 1 microlitre of sample with a buffer solution into pre-coated disposable cuvettes.
3. Optical spectroscopy on the sample, using a versatile bench top instrument with easy to use software.
4. Reading of results after 3 min measurement cycle directly reading out actual citrate concentration.

The sample is taken from the prostate gland – this is part of the biopsy procedure during clinical analysis in urology.

For more information, read the following PubMed abstracts:

• Croswell JM, Kramer BS, Kreimer AR, et al. Cumulative incidence of false-positive results in repeated, multimodal cancer screening. Ann Fam Med. 2009 May-Jun;7(3):212-22
• Prorok PC, Andriole GL, Bresalier RS, et al. Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Control Clin Trials 2000 Dec;21(6 Suppl):273S-309S.
• Hessels D, Schalken JA. The use of PCA3 in the diagnosis of prostate cancer. Nat Rev Urol. 2009 May;6(5):255-61
• Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007 Mar;18(3):581-92. Epub 2007 Feb 7.

Other resources:

• National Cancer Institute - Factsheet Prostate Cancer
• National Cancer Institute - About Prostate Cancer

Information for your patients:

• National cancer Institute: the online booklet What You Need To Know About™ Prostate Cancer to learn about prostate cancer symptoms, diagnosis, treatment, and questions to ask the doctor.

Fig. 1 : Range of citrate levels measured using the new optical probe

European specialists are joining forces to improve lung cancer treatment

Prevention, personalized therapies and closer collaborations between surgeons, medical oncologists and radiation oncologists will result in better outcomes for lung cancer patients and those at risk, a leading European expert says.

“Lung cancer is a complex disease. It is one of the most complex cancers, and the more we learn about the biology of the disease, the more we realize that improved cancer care will result from multidisciplinary treatment,” said Prof Robert Pirker, from the Medical University of Vienna, Austria (Spitalgasse 231090 Wien 9., Alsergrund, Wien, Austria). Prof Pirker is co-chair of the scientific committee of a new medical conference, the European Multidisciplinary Conference in Thoracic Oncology (EMCTO), being held for the first time this year, 1-3 May, at the Palazzo dei Congressi in Lugano, Switzerland.

The conference aims to further clinical and scientific cooperation between disciplines to help in the fight against lung cancer. Designed as a regular multidisciplinary, educational meeting, the organizers feel that the meeting may help strengthening general knowledge and providing an updated overview of prevention, screening, diagnosis, treatment modalities and results of translational research. One of the goals of the organizers is to facilitate interaction between the specialties in order to promote an integrated approach to diagnosis and treatment of chest tumors and to strengthen European cooperation and scientific exchange in multidisciplinary management of lung cancer.

A common cancer
Lung cancer is the most common cancer in the world. In men, the highest incidence rates are seen in Europe (especially eastern Europe) and North America. In women, high incidence rates are found in North America and in Europe, particularly in northern and western Europe.

Role of tobacco and smoking
Tobacco smoking is well established as the main cause of lung cancer and about 90% of cases are thought to be tobacco related. There is a clear dose-response relation between lung-cancer risk and the number of cigarettes smoked per day, degree of inhalation, and age at initiation of smoking. Researchers have noted that someone who has smoked all his life has a 20 -30 times greater risk of getting lung-cancer than a non-smoker. The link between tobacco-use and smoking is further emphasized by the fact that the risk of lung cancer decreases with time since smoking cessation.

Research has also shown that while the incidence of lung cancer among men in many Western European countries has been decreasing since the 1980s, the age-adjusted rate for men in other European countries increased at least until the 1990s. Among women this peak in incidence had not been reached in the 1990s. At the same time, the proportion of adenocarcinoma in both men and women has been increasing over time. The most likely explanation for this trend is the shift to low-tar filter cigarettes.

Screening Emphasized
Since the early 2000’s there has been renewed interest in screening because spiral computerized tomography (CT) can detect small asymptomatic lesions more effectively than conventional radiography. Although cure rates for such lesions are very good, there is to date no evidence for effectiveness of mass-screening strategies.

Targeted therapies
Over the past 5 years, researchers have established that for patients with operable cancer, surgery followed by chemotherapy can result in good outcomes. Now, large clinical trials are beginning to evaluate that adding molecular targeted therapies can further improve the chance of a successful outcome for some patients. In addition, doctors are now attempting to refine their treatments based on the clinical characteristics of individual patients, and based on the molecular profile of their tumor.

“More sophisticated and complex treatments require more cooperation,” Prof Pirker says. “That is one of the reasons why we have organized this conference. We believe the result will be better outcomes for lung cancer patients.”

For patients with metastatic disease, targeted therapies have already entered clinical practice or have shown survival benefit in clinical trials. Combinations of chemotherapy and radiotherapy are also improving outcomes of loco-regional non-small-cell lung cancer. “Cure is now possible in about 15% to 20% of patients whose disease can be treated in this way,” adds Prof Jean-Paul Sculier, from Institut Jules Bordet in Brussels, Belgium. (121 Boulevard de Waterloolaan, Bruxelles 1000 Brussel 121 Boulevard de Waterloolaan, Bruxelles 1000 Brussel, telephone +32 254 1311). Prof Sculier will chair a session on treating advanced disease at the conference.

During the European Multidisciplinary Conference in Thoracic Oncology Research groups will present new data that reflect these developments, including:

• A study comparing radiotherapy alone to sequential chemotherapy and radiation in locally advanced non-small-cell lung cancer, plus a correlation of gene expression level with survival (UK).
• Promising results from a study of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small-cell lung cancer (Poland).
• Confirmation that EGFR mutations (deletion in exon 19, missense L858R) are the most important predictors of sensitivity to tyrosine-kinase inhibitor targeted therapies (Italy)
  

Barbara Zolty from the World Health Organization (Avenue Appia 20 1211 Geneva 27 Switzerland telephone +4122791211) will also highlight the importance of preventing lung cancer as the first and foremost weapon against lung cancer. Ms Zolty will speak about the WHO Tobacco-Free Initiative with an enlightening keynote lecture entitled “A thousand seconds, a thousand lives.”

The EMCTO Conference is co-organized by the European Society for Medical Oncology (ESMO), the European Society for Therapeutic Radiology and Oncology (ESTRO), the European Society of Thoracic Surgeons (ESTS) and the European Respiratory Society (ERS)

For more information also read:

• Janssen-Heijnen ML and Coebergh JW, The changing epidemiology of lung cancer in Europe, Lung Cancer. 2003 Sep;41(3):245-58 )
  

'Coping with Cancer from the Outside In', a new educational campaign

Biotechnology pioneer Amgen (One Amgen Center Drive Thousand Oaks, CA 91320-1799, Phone 1-805-447-1000) and ONSEdge a subsidiary of the Oncology Nursing Society (ONS), today announced that they will partner alongside celebrity make-up artist and cancer survivor Jan Ping to support a new educational campaign, Coping with Cancer From the Outside In. The initiative is aimed at educating oncology nurses about the skin-related side effects associated with epidermal growth factor receptor (EGFR) inhibitors that are used to treat metastatic colorectal, lung, pancreatic, and head and neck cancers.

Therapy
The EGFR plays a critical role in the control of cellular proliferation, differentiation, and survival. Abnormalities in signaling of the EGFR pathway have been found in a wide range of cancers.

EGFR inhibitor therapy aims to interrupt tumor growth by disrupting signals sent from the epidermal growth factor receptor, which is found on the surface of some cancer cells. Because EGFR is also present on other normal cells in the body, including skin cells, skin rash occurs in up to 90 percent of patients undergoing treatment with an EGFR inhibitor. This can be serious and potentially life threatening. Further, in its mild-to-moderate state, skin rash can cause patients physical discomfort and take an emotional toll, affecting body image. For most patients these side effects are mild, but moderate or severe toxicities that lead to dose modification or interruption develop in 8-17 percent of patients. Other appearance-related side effects include nail changes, skin cracking and hair disorders.

A new educational campaign
The new campaign will kick off at the 34th Annual ONS Congress on April 30, 2009 in San Antonio, Texas, where leading oncology experts and Jan Ping will host an informational seminar on coping with the appearance-related side effects that can accompany EGFR inhibitor treatments, along with other tips nurses can provide to both male and female patients for looking their best during treatment.

Seminar attendees will be invited to a meet-and-greet reception with Jan Ping and guest
speakers, and will be supplied with educational materials. Jan Ping, an Emmy® Award-winning make-up artist known for her work on E! Entertainment's Chelsea Lately Show and the Tyra Banks Show, and her work with celebrities such as Cindy Crawford and Warren Beatty, was diagnosed with breast cancer at age 45 and knows from her own experience that a patient's body changes while undergoing cancer treatment. But despite her altered appearance, Ping maintained a positive outlook, and she will lend her beauty and skin care expertise to the campaign to help patients feel confident about their appearance during treatment. "I'm excited to be taking part in an important program that provides oncology nurses with everyday tips they can teach patients to boost confidence during a difficult time."

Following the campaign launch at the Annual ONS Congress, local training seminars will also be held in the second half of this year in New York City, Los Angeles, and Miami.

• Follow-up and action points
  When talking to your patients, explain that a preventive skin treatment reduces the adverse effects of EGFR inhibitor therapy.

• More information
  For additional information on the dermatologic effects of EGFR inhibitors, download the nurse handbook - Coping With Cancer from the Outside In – Tips and Tools for the Oncology Nurse, provided to you courtesy of Amgen.

• Helpful links
  You Tube: The 34th Annual Oncology Nursing Society Congress, San Antonio, TX. Includes the keynote presentation by Geralyn Lucas
  
• Published articles
  Ivanov VN, Hei KT. Combined treatment with EGFR inhibitors and arsenite upregulated apoptosis in human EGFR-positive melanomas: a role of suppression of the PI3K-AKT pathway Oncogene 2005 Jan 20;24(4):616-26( Published online 6 December 2004)
  PubMed
  
• Ortega E, Marti RM, Yeramian A, Sorolla A, et al. Targeted therapies in gynecologic cancers and melanoma. Semin Diagn Pathol. 2008 Nov;25(4):262-73. Review.
  
• Wang W, Edington HD, Jukic DM, Rao UN, et al. Impact of IFNalpha2b upon pSTAT3 and the MEK/ERK MAPK pathway in melanoma. Cancer Immunol Immunother. 2008 Sep;57(9):1315-21. Epub 2008 Apr 3.

Melanoma Research Foundation Launches Digital Resources, leveraging online tools to reach consumers during Melanoma Awareness Month

As part of Melanoma Awareness Month this May, the Melanoma Research Foundation (MRF -) the largest independent, national organization devoted to melanoma in the United States committed to the support of medical research in finding effective treatments and eventually a cure for melanoma, is launching three new resources to reach the online community. Now digital users can learn more about melanoma and access tools to fight this deadly disease through Facebook, Twitter and the MRF Melanoma Messengers programs.

"Melanoma Awareness Month exists because this disease is not sufficiently in the public's mind. If we are going to stop melanoma, we need to extend our reach to include young people, who have the fastest rising incidence rates." said Tim Turnham, executive director of the MRF. "We are really excited about the potential of these online programs to reach Americans where they live, work and play."

Created as a grassroots, volunteer program, the MRF Melanoma Messengers toolkit will enable individuals to join a national network dedicated to supporting medical research, educating patients and physicians, and acting as an advocate for the melanoma community. The additional social networking sites, including Facebook and Twitter, will enable volunteers to stay connected, share tips and offer support to others.

"Our Facebook, Twitter and MRF Melanoma Messengers programs give people the tools and resources they need to raise awareness in their local and online communities," continued Turnham. "Whether you are a fan, a tweeter or a volunteer, it's now easier than ever before to show your support for those affected by this deadly disease."

"This month, the MRF's Messengers will be involved in nearly 30 different fundraising events and activities across the country to raise money to find a cure, including our first 'Melanoma Tweetments' fundraiser," said C. Randy Lomax, chairman of the MRF's board of directors. "Individual Twitter users can make a difference by sending tweets about melanoma to their followers and donating a few dollars to fund melanoma research."

The Most Deadly type of Skin Cancer
Melanoma, the most deadly type of skin cancer, claims the life of approximately one American every hour and is the fastest growing cancer in the United States and worldwide. It strikes men and women of all ages, all races and all skin types. In fact, with a one in 50 lifetime risk of developing melanoma, more than 62,000 Americans were expected to be diagnosed with the disease in 2008, resulting in an estimated 8,400 deaths. Melanoma is the most common form of cancer for young adults 25- to 29-years-old and the second most common cancer in adolescents and young adults 15- to 29-years-old.

In its early stages, melanoma can be successfully removed and monitored by regular skin screenings. However, the disease is deadly in its most advanced stages, as few treatment options exist. The median life expectancy for patients with advanced melanoma is less than one year and existing therapies have not improved survival in more than a decade.

Social media users can stay up-to-date on what's going on at the MRF and in the melanoma community by following @curemelanoma on Twitter and becoming a fan of the Melanoma Research Foundation and inviting friends to support the cause on Facebook

• MRF's Twitter Page
• MRF's Facebook Page
• MRF's Facebook Cause
• MRF's Melanoma Messengers Group on Facebook