Canadian Cancer Trials Group Bulletins


Recent Publication and Press Release

The primary results of Canadian Cancer Trials Group OV.16 -- A Phase III Study of Cisplatin plus Topotecan Followed by Paciltaxel plus Carboplatin versus Paclitaxel Plus Carboplatin as First Line Chemotherapy in Women with Newly Diagnosed Advanced Epithelial Ovarian Cancer -- were recently published in the Journal of the National Cancer Institute and was selected by the Journal to be highlighted to the media.

The study found that topotecan and cisplatin, followed by carboplatin and paclitaxel, were more toxic than carboplatin and paclitaxel alone, but without improved efficacy. Carboplatin plus paclitaxel remains the standard of care for advanced epithelial ovarian cancer.

Following are the full citation, link to the article and editorial and press release, and the text of the release:

Hoskins P, Vergote I, Cervantes A, Tu D, Stuart G, Zola P, Poveda A, Provencher D, Katsaros D, Ojeda B, Ghatage P, Grimshaw R, Casado A, Elit L, Mendiola C, Sugimoto A, D'Hondt V, Oza A, Germa JR, Roy M, Brotto L, Chen D, Eisenhauer EA. Advanced ovarian cancer: Phase III randomized study of sequential cisplatin-topotecan and carboplatin-paclitaxel vs carboplatin-paclitaxel (ONLINE). J Natl Cancer Inst 2010.

Following is the press release:

Adding Topotecan to Standard Treatment for Ovarian Cancer Does Not Improve Progression-Free Survival

Adding Topotecan to carboplatin plus paclitaxel, the standard treatment for ovarian cancer, does not improve progression-free survival in patients, and leads to greater toxicity, according to a study published online in The Journal of the National Cancer Institute.

Cisplatin plus paclitaxel, and carboplatin plus paclitaxel, are the most widely accepted first-line regimens for advanced epithelial ovarian cancer. Still, most women relapse and die of from their disease. One possible solution that has been tried is to add a third agent, such as topotecan, which has shown activity in the treatment of recurrent disease. However, combining topotecan with carboplatin plus paclitaxel as a triplet therapy is problematic because of bone marrow toxicity. So, to integrate topotecan into the standard regimen researchers tested sequential doublets of cisplatic plus topotecan followed by carboplatin plus paclitaxel.

To determine whether topotecan could be effective when added to standard treatment, the Canadian Cancer Trials Group at Queen's University in Kingston, Canada, together with the European Organization for Research and Treatment of Cancer - Gynecologic Cancer Group, European Union and the Grupo Espańol de Investigación en Cáncer de Ovario (GEICO), Spain conducted a phase III randomized study of 819 women aged 28-78 with newly-diagnosed stage IIB or more advanced, ovarian cancer. Principal investigator Paul Hoskins, MD, of the BC Cancer Agency in Vancouver, and colleagues from Canada and Europe enrolled patients who were randomly assigned to one of two study groups: the first arm received cisplatin and topotecan, followed by carboplatin and paclitaxel; the second arm received carboplatin and paclitaxel.

The researchers found that after a median follow-up of 43 months, 650 patients had disease progression and 406 had died. The progression free survival of patients in the first arm was no better than those in the second (standard) arm, indeed it was only 14.6 months versus 16.2 months. Furthermore, although survival data was not mature, there is no evidence to date patients receiving topotecan had improved survival (median overall survival of 42.3 and 42.1 months in the first and second arms of the study respectively). Patients in the first arm also had more toxicity than those in the second. The common side effects included gastrointestinal symptoms, myelosuppression, neurological toxicity and myalgia. Patients in the first arm had more myelotoxicity, nausea and vomiting, while patients in the second had mo rs concluded that carboplatin plus paclitaxel remains the best standard of care for epithelial ovarian cancer stage IIB or greater. They write, "The most sensible explanation for this lack of additional benefit is that the topotecan does not have sufficient cytotoxic impact on cells that are truly resistant to platins or taxanes."

Furthermore, they explain that a drug such as topotecan needs to be effective in the refractory setting -- when the cancer grows during treatment -- and not just in the resistant setting -- when it recurs shortly after the end of treatment. They write, "Further cytotoxic drugs need to be able to convincingly kill truly refractory cells before being added to the preexisting standard drug or drugs for efficacy testing."

In an accompanying editorial, William P. McGuire, MD, of the Weinberg Cancer Institute at Franklin Square Hospital Center, writes that the trial conducted by Hoskins provides further confirmation of the inactivity of topotecan to treat standard ovarian cancer. He writes, "In the end, neither the dose of topotecan, sequence of drug administration, nor platinum compound used in combination made any difference."

McGuire also points out the emergence of targeted therapies to treat ovarian cancer instead of cytotoxic agents. He writes, "Clearly, the lack of any benefit from adding topotecan gemcitabine, or pegylated liposomal doxorubicin to the platinum/taxane in the intergroup trial has signaled the need to try new approaches."

The Canadian Cancer Trials Group (Canadian Cancer Trials Group) is a cancer clinical trials cooperative group that conducts phase I-III trials testing anti-cancer and supportive therapies across Canada and internationally. It is one of the national programmes and networks of the Canadian Cancer Society Research Institute (CCSRI), and is supported by the CCSRI with funds raised by the Canadian Cancer Society (CCS). The Canadian Cancer Trials Group's Central Office is located at Queen's University in Kingston, Ontario, Canada.

The ultimate goal of the European Organization for Research and Treatment of Cancer (EORTC) is to improve the standard of cancer treatment through the testing of more effective therapeutic strategies based on drugs, surgery and/or radiotherapy that are already in use, and also through the development of new drugs and other innovative approaches. This is accomplished mainly by conducting large, multicentre, prospective, randomized, phase III clinical trials. In this way, the EORTC facilitates the passage of experimental discoveries into state-of-the-art treatments. The EORTC Headquarters is based in Brussels, Belgium, European Union, from where its various activities are coordinated and run.

GEICO, the Spanish group for research in ovarian cancer, was founded in 1999 with the aim of stimulating and developing clinical research in ovarian and gynecological malignancies, as well as educational activities. It is made up by more than 70 Spanish hospitals and is integrated in the Gynecological Cancer Intergroup (GCIG) structure.