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.

Dexamethasone can Eliminate One-Third of All Relapses in Childhood Acute Lymphoblastic Leukemia

The results from a study conducted by Martin Schrappe, MD, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany showed that the use of dexamethasone, a corticosteroid commonly used to treat inflammation of the skin, joints, lungs and other organs, in the induction phase of combination chemotherapy led to a one-third reduction in the risk of relapse as compared with prednisone, the standard corticosteroid therapy. These results translated into a significant benefit in terms of event-free survival in children with acute lymphoblastic leukemia. Schrappe presented these results during the 50th Annual Meeting of the American Society of Hematology (ASH) in San Francisco, CA (December 6 – 9).

Dexamethasone was associated with a greater risk of severe side effects, mainly invasive infections; hence, more intensive clinical monitoring and, in particular, early antimicrobial therapy in patients should be implemented to preserve the advantage of using dexamethasone, rather than prednisone, as part of induction therapy.

Following a pre-phase treatment regimen of prednisone and intrathecal methotrexate, a total of 3,655 children (ages 1 to 17) from Germany, Italy, Austria, and Switzerland with acute lymphoblastic leukemia were randomized to receive induction therapy consisting of either prednisone (60 mg/m2/d) or dexamethasone (10 mg/m2/d) in addition to vincristine, daunorubicine, and L-asparaginase combination therapy. Post-induction therapy was also given to patients.

Six-year event-free survival reached 84.1 percent in patients who received dexamethasone as compared with 79.1 percent of those who received prednisone in the induction phase. The six-year cumulative incidence of relapse was 11 percent and 18 percent for patients randomized to dexamethasone and prednisone, respectively. The difference between the two groups was observed for bone marrow relapses (8 percent versus 12 percent), central nervous system relapses (2 percent versus 4 percent), and other relapses (2 percent versus 3 percent) in dexamethasone as compared with prednisone.

Higher toxicity was seen in those treated with dexamethasone. The cumulative incidence for death in the induction phase was 2 percent for dexamethasone compared with 0.9 percent for prednisone; however, the cumulative incidence of death during remission was similar between the two treatment groups (2 percent for dexamethasone and 1.6 for prednisone).

Although dexamethasone was associated with a greater risk of severe toxicity, the results of the study show that it leads to a marked reduction of the risk of relapse, translating this into a significant benefits. This was most evident in patients with in vivo sensitivity to the prednisone prephase, while the efficacy of dexamethasone in poor responding patients was not convincing. The researchers conclude that in the future, more intensive clinical monitoring and early anti-infective interventions could render the advantage of using dexamethasone even more evident. They also believe that other, potentially toxic, agents such as anthracyclines may be limited in induction for carefully selected subgroups of patients with the aim of limiting early or late toxicities.

For more information, read:
Schrappe M, Zimmermann M, Möricke A, Mann G, et al. Dexamethasone in Induction Can Eliminate One-Third of All Relapses in Childhood Acute Lymphoblastic Leukemia: Results of an International Randomized Trial in 3,655 Patients (Trial AIEOP-BFM ALL 2000) (Oral Session), Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #7

Also read PubMed abstracts:
Möricke A, Reiter A, Zimmermann M, Gadner H, et al. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95.Blood 2008 May 1;111(9):4477-89. Epub 2008 Feb 19.