A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study

Abstract

Objectives After surgical debulking and volume-directed irradiation of the pelvis/para-aortic lymph nodes, treatment was randomized to compare recurrence-free survival (RFS) and toxicity between two chemotherapy regimens for the treatment of women with advanced stage endometrial carcinoma. Methods Treatment was randomized between 6 cycles of cisplatin [C] (50 mg/m2) and doxorubicin [D] (45 mg/m2) with or without paclitaxel [P] (160 mg/m2). Initially in paclitaxel treated patients and, after May 2002, all patients received granulocyte growth factor with each cycle. Results Of 659 patients enrolled following surgery, 552 eligible patients were randomized to chemotherapy after irradiation. Accrual closed to Stage IV patients in June, 2003. Approximately 80% completed six cycles of chemotherapy. Three deaths resulted from bowel complications and one death was due to renal failure. Hematologic adverse events, sensory neuropathy and myalgia, were more frequent and severe in the paclitaxel arm (p< 0.01) which was confirmed by Quality of Life assessments. Percentage of patients alive and recurrence-free at 36 months was 62% for CD vs. 64% for CDP. The hazard of recurrence or death relative to the CD arm stratified by stage is 0.90 (95% CI is 0.69 to 1.17, p=0.21, one-tail). However, in subgroup analysis, CDP was associated with a 50% reduction in the risk of recurrence or death among patients with gross residual disease (95% CI: 0.26 to 0.92). Stage, residual disease, histology/grade, positive para-aortic node and cytology, pelvic metastases and age were significantly associated with RFS. Conclusion The addition of paclitaxel to cisplatin and doxorubicin following surgery and radiation was not associated with a significant improvement in RFS but was associated with increased toxicity.

Does the progression‐free interval after primary chemotherapy predict survival after salvage chemotherapy in advanced and recurrent endometrial cancer?

“…Even in patients with minimal residual disease, such as those treated on Gynecologic Oncology Group protocols 122 and 184, the recurrence rate still approaches 50%. 2,24 As a result, a sizable population exists for whom active second-line therapy is needed. How to best treat this population is unclear.…”

Salvage intraperitoneal chemotherapy for relapsed type II endometrial cancer: A pilot case-control study

“…Currently, no specific tailored treatment exists for relapsed type II endometrial cancer due to the rarity of this disease. Still, the current gold standard treatment for relapsed type II endometrial cancer is the same as that for relapsed type I endometrial cancer, which is based on a series of published phase III randomized trials that focused on the efficacy of chemotherapy (7,(21)(22)(23)(24)(25). However, given the apparent differences in clinical behavior between type I and type II endometrial cancers, it has been suggested that treatments should be tailored according to the histologic type.…”

Present status and future direction of clinical trials in advanced endometrial carcinoma

“…1 The GOG Corpus Committee is charged with the responsibility of protocol development for advanced endometrial carcinoma. The statistical updates contained in the six month statistical reports, now readily available on the GOG web site, are reviewed at each six month meeting.…”

“…Stage (IV vs III), residual disease (gross vs microscopic), extended field radiation (yes vs no), histology/grade (serous vs adenocarcinoma), positive para-aortic node (yes vs no), positive cytology (yes vs no), pelvic metastases (serosa/adnexa yes or no) and age (risk increases with age) were significantly associated with RFS with the most high risk categories of clear cell/papillary serous histology and grade 3 adenocarcinoma. 1 Or should GOG184R be a duplicate ten year trial with different chemotherapy in the exact same population? 11.…”

“…Yet, recent findings in GOG184 indicate that multiple risk factors noted at the time of surgical staging could lead to concurrent clinical trials that could be completed expeditiously rather than a subsequent ten year long phase III trial including all the various risk subgroups of patients. 1 This review is a focus on the accomplishments of the Gynecologic Oncology Group (GOG) in advanced endometrial carcinoma with an emphasis on future challenges. Is it time for a different clinical trial approach?…”