Novel Cancer Drug Test May Results in Safer and More Effective Clinical Trials

A group of scientists from Hamburg may have taken a big step towards more effective cancer drug development. Dr Ilona Schonn, Director of Cell Culture Research at Indivumed GmbH, a company specialized in the analysis and procurement of highly standardized tissue samples and data of tumor patients, told the audience at Europe’s largest cancer congress, the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20 – 24 in Berlin, Germany, that they had developed a preclinical drug test platform that would enable researchers to analyze tumor tissue for individual patient drug responses on the molecular level.

To date most tests for drug metabolism and toxicity testing have used tissue slices of normal organs like liver, kidney and lung. The new test was created specifically for oncology drug testing and uses tumor tissues from colorectal and lung cancer patients.

A major problem of drug development at present is the inability to extrapolate response in preclinical cell models to patients. “Approximately 90% of clinical trials fail because the drugs used are too ineffective or too toxic,” explained Dr Schonn. “Not only does this result in unacceptably high costs for drug development, but it also exposes patients to risks from toxicity or simply wastes their time in testing a substance which proves to be ineffective.”

The problem arises from the fact that patients respond individually to drugs. In addition, each tumor consists of a variety of different cancer cells that interact in different ways with the framework of individual non-tumor cells, resulting in highly variable growth behavior and response to drugs. Dr Schonn and her team set out to try to develop a drug test that would eliminate these problems and provide an accurate model of individual patient response.

“Based on freshly cultivated intact tissue from surgically treated cancer patients we are now able to analyze numerous tumors from different patients, to identify differences in drug response between those patients, and to understand variations of response in cell subtypes within one tumor,” said Dr Schonn.

The new test allows scientists to translate findings from commonly used cell lines to a preclinical model which is as close as possible to using the same drug in the clinical setting, thus enabling a better estimate of the number of patients who are likely to respond to the treatment. It also helps to identify biomarkers that can predict drug response for patients entering a clinical trial, allowing researchers to include only those patients whose participation will provide a significant answer to the question being asked.

“Together with all the clinical patient data and several analytical test systems such as signaling pathway analysis, we have been able to characterize individual tumors in more detail. This will improve the understanding of drug effects and treatments, a step forward towards the goal of individualized cancer therapy,” she said. “The test is of particular interest to pharmaceutical companies because it allows the analysis of samples from meaningful number of patients with different tumors in a short period of time, and can, therefore, accelerate progression of a potential new treatment to clinical trials.”

In addition, it can help gain more knowledge about the mode of action of a new compound in patients, and identify optimal disease areas, for example tumors with particular mutations or over-expression of target receptors, and dosage.

To date the test has only been validated in colon, non-small cell lung (NSCLC), and breast cancer tumors but there is no reason to think that it would not be equally accurate in other solid tumor types, the scientists say.

“Because the test allows us to maintain the complex environment of the primary cancer tumor, we believe that it holds out great promise for the quick and effective elucidation of response to anticancer drugs,” said Dr Schonn. “We hope to be able to apply it to a growing number of drugs emerging from the labs of pharmaceutical companies to help to shorten development time and to make clinical trials both more efficient and safer for patients.”

The test can analyze numerous tumors from different patients, identify the patients’ diverse reactions to the test compounds and elucidate their varying effects on cell subtypes within the same tumor. Says Prof Dr Hartmut Juhl, CEO and founder of Indivumed. “In the long run, our test paves the way to personalized medicine, because it helps to understand and to embrace the individual reactions of the patients to a certain therapy.”

For more information:

• Abstract no: 1013, Basic Science/Translational Research poster discussion, Wednesday 17.00 – 18.00 hrs CEST (Hall 14.2)

No survival benefit with treatment based on rising CA125 blood levels in Recurrent Ovarian Cancer

There appears to be no survival advantage to treating ovarian cancer relapse based on rising CA125 levels, compared with waiting for symptoms. This is the conclusion from a study that was featured during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), the world’s leading professional organization representing physicians who care for people with cancer.

A team of researchers, lead by Gordon J. Rustin, MD professor of oncology at Mount Vernon Cancer Center, Hertfordshire, United Kingdom, reported that starting treatment immediately for an ovarian cancer relapse based on CA125 protein levels found in the blood does not improve overall survival, compared with delaying treatment until symptoms arise. The findings should allow women to avoid the anxiety and cost associated with frequent blood testing and the toxicity of early treatment.

“Women who’ve completed ovarian cancer treatment often worry about a relapse, and they undergo frequent blood tests for CA125 in the hope of catching it early,” Rustin said.

CA125 often rises several months before women with OC have symptoms or clinical signs of relapse. This study (MRC OV05/EORTC 55955 trials), conducted by the MRC/NCRI and EORTC Gynae Cancer Intergroups, was designed to determine whether there were benefits from early treatment based on a confirmed elevation of CA125 levels versus delaying treatment until clinically indicated.

“We thought that delaying chemotherapy might make overall quality of life worse, due to the symptoms of ovarian cancer, but this was not seen in women on this trial. Since there is no benefit from early chemotherapy, patients may choose to avoid the inconvenience and anxiety associated with frequent retesting for CA125 levels as well as unnecessary early initiation of treatment for relapse,” Rustin explains.

CA125 is a marker of growth for several cancers, including ovarian cancer, and is measured by a blood test. Women who have undergone treatment for ovarian cancer may have their CA125 levels tested as often as every three months for several years after initial treatment.

In this study, investigators compared overall survival between 265 women with ovarian cancer in remission after initial chemotherapy who began second-line chemotherapy after experiencing a rise in CA125, and 264 women with rising CA125 whose treatment was delayed until symptoms of relapse appeared (such as pelvic pain or bloating).

Even though the early treatment group started second-line chemotherapy an average five months before the delayed treatment group, overall survival was the same between both groups: 41 months since completion of first-line chemotherapy.

The researchers added that this trial provides important information that will help women make informed choices about their follow-up and treatment. They can be reassured that treatment can safely be delayed until symptoms develop.

ASCO 2009 abstract:

• G. J. Rustin, M. E. van der Burg, on behalf of MRC and EORTC collaborators. A randomized trial in ovarian cancer (OC) of early treatment of relapse based on CA125 level alone versus delayed treatment based on conventional clinical indicators (MRC OV05/EORTC 55955 trials). Abstract P1. D2 Plenary Presentation, Sunday, May 31, 2009 1:45 PM EDT, Level 2, Westhal, Plenary Session.

For more information, read these PubMed abstracts:

• Sivanesaratnam V. Third S. S. Ratnam Memorial Lecture 2007. Ovarian cancer: Is there hope for women? J Obstet Gynaecol Res. 2009 Jun;35(3):393-404.
• Gupta D, Lis CG, Vashi PG, Lammersfeld CA. Impact of improved nutritional status on survival in ovarian cancer. Support Care Cancer. 2009 May 31. [Epub ahead of print]
• Turgut O, Tandogan I, Yilmaz MB, Gul I, Gurlek A. CA125 levels among patients with advanced heart failure: An emerging independent predictor for survival. Int. J Cardiol. 2009 May 13. [Epub ahead of print].

Help your patients understand:

• For consumer-oriented information about the studies in this article, please refer your patients to ASCO’s patient website.

Photo and illustration courtesy of the American Society of Clinical Oncology.