Study Demonstrates Hycamtin® - Cisplatin Regimen Improves Survival in Advanced Cervical Cancer
No Additional "Cost" to Patients' Quality of Life with Combo Therapy
MISSISSAUGA, ON (March 4, 2004) -- Results of a Gynecologic Oncology Group (GOG) study, presented last month at the Society of Gynecologic Oncologists Annual Meeting on Women's Cancer, showed the combination of Hycamtin® (topotecan HCl for Injection) and cisplatin significantly improved survival in women with recurrent cervical cancer compared to single-agent cisplatin. The combination also showed superiority over cisplatin alone in overall response rate and progression-free survival.
The randomized, multicenter Phase III trial enrolled women with measurable, histologically-proven stage IVB recurrent or persistent carcinoma of the cervix with a GOG performance status of 0-2 who had recovered from the effects of prior surgery, radiation or chemoradiation. The overall response rate was 13 per cent for cisplatin alone and 27 per cent for cisplatin plus Hycamtin, a statistically significant difference (p=0.004). Median progression free survival was 2.9 months and 4.6 months and median survival was 6.5 and 9.4 months, respectively.
"This is the first regimen to demonstrate a survival advantage over single agent cisplatin," said Harry J. Long III, M.D., Associate Professor of Oncology at Mayo Clinic College of Medicine in Rochester, Minn., who presented the survival analysis. "These data suggest that by combining cisplatin with Hycamtin, we may have taken a step forward in our efforts to extend the lives of women with advanced cancer of the cervix."
Quality of Life Assessments
Patients enrolled in both arms of the study provided quality of life data prior to their first (baseline), second and fifth doses, and at nine months. Quality of life outcomes allow one to estimate the "cost" of increased response rates and survival. This measures critical endpoints when an add-on therapy increases side effects such as myelosuppression, neurotoxicity and alopecia. Quality of life is prognostic of survival in this setting.
The investigators reported that the addition of Hycamtin to cisplatin appeared to have no impact on patient quality of life. Throughout therapy, assessment scores remained stable with no statistical differences appearing between treatment groups at any time point in the treatment of advanced or recurrent cervical cancer.
Major toxicities (Grade 3 and 4) were more frequent in the combination arm than in the single agent arm and included: neutropenia (70 per cent versus 1 per cent, respectively); anemia (37 per cent versus 23 per cent); febrile neutropenia/infection (16 per cent versus 8 per cent); nausea (13 per cent versus 8 per cent); emesis (14 per cent versus 8 per cent); and metabolic toxicity (12 per cent versus 10 per cent).
"Although, as expected, there was an increase in reported toxicities with the two-agent regimen, the treatment experience, in terms of quality of life, was equivalent to single-agent therapy from the patients' perspective," said Dr. Long.
"When we evaluate new therapeutic regimens for advanced disease, we must consider not just the extension of life but the quality of this additional time as well," said Dr. Diane Provencher, Senior Clinical Researcher, Chief of Division of Gynecology Oncology, Centre de recherche du CHUM, Hôpital Notre-Dame, Montreal, Québec. "In this study, we observed that the survival advantage offered by this combination did not come at the expense of patients' quality of life."
About the Gynecologic Oncology Group
The GOG is an international non-profit organization dedicated to clinical research in the field of gynecologic cancer. The purpose of the GOG is to improve the treatment of gynecologic cancer. These goals are addressed through research encompassing surgery, radiation therapy, chemotherapy, pathology, immunology and/or gynecologic nursing. To promote this mission, the GOG receives support from the National Cancer Institute (NCI) of the National Institutes of Health. More information is available at www.gog.org.
About Hycamtin
Hycamtin (topotecan HCl for Injection) is currently marketed in Canada by GlaxoSmithKline. It belongs to a class of drugs known as the topoisomerase I (topo-I) inhibitors. Topo-I is a naturally produced protein essential for cell division in both normal and cancer cells. Interaction between topo-I and Hycamtin results in permanent damage to the cell's genetic material and the death of dividing cancer cells. Hycamtin is indicated for the treatment of small cell lung cancer sensitive disease after failure of first-line chemotherapy defined as recurrence at least 60 days after first line chemotherapy, and for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy. Hycamtin is not approved for use in cervical cancer or in combination with cisplatin in Canada.
Important Safety Information
Hycamtin (topotecan HCl for Injection) can suppress the body's ability to produce disease fighting white blood cells, a condition known as neutropenia. In addition, the amount of clotting cells can decrease (thrombocytopenia). Generally, Hycamtin has a mild to moderate non-hematologic toxicity profile. Side effects include nausea, vomiting, diarrhea and hair loss (alopecia).
Prevalence
According to the National Cancer Institute of Canada, there were an estimated 1,400 new cases of cervical cancer diagnosed in 2003 and an estimated 420 deaths attributed to cervical cancer. This accounts for approximately two per cent of estimated new cases of cancer in females in Canada, and approximately 1.3 per cent of estimated new deaths.1
About GlaxoSmithKline
GlaxoSmithKline Inc. - one of the world's leading research-based pharmaceutical and health-care companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. In Canada, GlaxoSmithKline is a top 20 investor in Canadian research and development, contributing more than $100 million annually. The company is also among the top 10 corporate charitable donors and is recognized as one of the 50 best companies to work for in Canada. For more information, visit www.gsk.ca.
For more information please contact:
Alison Steeves
GlaxoSmithKline
(905) 819-3363
Laura Pagnotta/Celeste Chiasson
NATIONAL PharmaCom
(416) 848-1434/1446
References:
- National Cancer Institute of Canada: Canadian Cancer Statistics 2003. Surveillance and Risk Assessment Division, CCDPC, Health Canada.