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Study: Hycamtin-Cisplatin Combinatin Improves Survival Over Cisplatin Alone in Advanced Cervical Cancer

SAN DIEGO, Feb. 9 /PRNewswire/ -- According to results of a Gynecologic Oncology Group (GOG) study, presented at the Society of Gynecologic Oncologists (SGO) Annual Meeting on Women's Cancer, 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 control arm. The combination also showed superiority over cisplatin alone in overall response rate and progression-free survival [SGO Abstract #125]. Hycamtin is not indicated or approved for use in cervical cancer or in combination with cisplatin.

"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."

In a second paper on the same study, researchers reported that there were no statistically significant differences in quality of life between the two treatment groups, as measured by four different patient self-assessment tools [SGO Abstract # 451].

"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 Bradley J. Monk, M.D., Assistant Professor, University of California Medical Center, Irvine. "We were gratified to observe that the apparent survival advantage offered by this combination did not come at the expense of patients' quality of life."

Hycamtin plus Cisplatin Improved 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. Patients were originally randomized into three arms: single-agent cisplatin (50 mg/m2 q 3 weeks), cisplatin plus Hycamtin (Hycamtin 0.75 mg/m2 d1-3 plus cisplatin 50 mg/m2 d1 q 3 weeks), or MVAC, methotrexate, vinblastine, doxorubicin, and cisplatin (q 4 weeks). However, the MVAC arm was closed after 63 patients were enrolled due to excessive toxicity. The investigators reported data on 145 evaluable patients who received cisplatin alone and 147 who received the combination of cisplatin plus Hycamtin.

The overall response rate was 13 percent for cisplatin alone and 27 percent 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. Hazard ratios for progression free survival (0.76, p=0.014) and survival (0.76, p=0.017), also favored the combination regimen.

Major toxicities (Grade 3 and 4) were more frequent in the combination arm than in the single agent arm and included neutropenia (1 percent vs. 70 percent, respectively), anemia (23 percent versus 37 percent), febrile neutropenia/infection (8 percent versus 16 percent), nausea (8 percent versus 13 percent), emesis (8 percent versus 14 percent), and metabolic toxicity (10 percent versus 12 percent).

"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.

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. Four assessment methods were utilized, with patients completing the Functional Assessment of Cancer Therapy-Cervix (FACT-G and FACT-Cx), a treatment-specific Neuro-toxicity Subscale (NTX), the Brief Pain Inventory (BPI), and the UNISCALE (UNI) at each time point. Ninety-seven percent of questionnaires were completed at baseline, with 83 percent, 66 percent, and 55 percent completed at subsequent evaluations.

The investigators reported that the addition of Hycamtin to cisplatin appeared to have no impact on patient quality of life. There were no statistical differences in quality of life scores at baseline between the single-agent cisplatin group and the Hycamtin-cisplatin group. Throughout therapy, assessment scores remained stable with no statistical differences appearing between treatment groups at any time point.

Within treatment groups, baseline quality of life scores on the FACT-G and BPI questionnaires were significantly associated with patient age, with older patients having better quality of life and less pain. Along with performance status, these scores also appeared to be prognostic of survival.

"These data establish an important link between quality of life measurements and clinical endpoints," said Dr. Monk. "By demonstrating the prognostic value of baseline quality of life measurements, we've provided additional evidence that quality of life should be integrated into clinical trial design and therapeutic decision-making, not just considered separately."

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 http://www.gog.org/.

About Hycamtin

Hycamtin® (topotecan HCl for Injection) is currently marketed in the United States 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 and for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy. For more information and full prescribing information, visit http://www.hycamtin.com/.

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).

Source: GlaxoSmithKline

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