A randomized trial of cyclophosphamide and doxorubicin with or without cisplatin in advanced ovarian carcinoma. A gynecologic oncology group study

Abstract

A randomized clinical trial was conducted in women with bulky (suboptimal) Stage III and Stage IV ovarian carcinoma, using doxorubicin (Adriamycin) and cyclophosphamide with or without cisplatin. There were 440 evaluable cases, of which 227 had measurable disease. One hundred twenty of these latter patients were treated with cyclophosphamide and doxorubicin (CA), while 107 received cyclophosphamide, doxorubicin and cisplatin (CAP). The clinical complete response (CR) rate for CA was 26% (31/120) compared with 51% (55/107) for CAP (P = less than 0.0001). Of 23 CRs receiving CA who had a second-look laparotomy, only four were negative; of 39 CRs receiving CAP and a second-look, 13 were negative (not statistically significant). The response duration for patients with measurable disease (median 14.6 versus 8.8 months), progression-free interval for all patients (13.1 versus 7.7 months), and survival for patients with measurable disease (19.7 versus 15.7 months) showed a statistically significant advantage for CAP; however, there was no difference in survival of patients with nonmeasurable disease. Toxicity was more severe with CAP but was tolerable. Thus, the addition of cisplatin improves the chemotherapy of advanced ovarian carcinoma.

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

“…With the introduction of platinum to the ovarian cancer treatment paradigm, RRs and PFS markedly improved. 26 Although platinum agents, taxanes, and anthracyclines all appear to have activity, none to date have demonstrated the type of activity required to drastically change the duration of first PFS. In addition, the absence of additional active salvage agents limits the application of sequential salvage chemotherapy in this population, even if we were to prolong first PFS.…”

Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer

“…Cisplatin-based chemotherapy has played an important role in the treatment of ovarian cancer and has resulted in a substantially improved response rate of approximately 60%. 1,2 However, the overall survival of the advanced cancer has remained unimproved at around 20% because considerable numbers of patients harbor resistant or refractory tumor to chemotherapy. 3 The mechanism of cisplatin resistance is estimated to be multifactorial and it remains unclear how genetic events are associated with the resistance in ovarian cancer.…”

Estimation of expectedness: Predictive accuracy of standard therapy outcomes in randomized phase 3 studies in epithelial ovarian cancer

“…This coupled with improved access to standard therapy and surgery has resulted in survival gains both in the first‐line setting and among patients with recurrent disease. In contrast to trials performed in the early 1980s, in which the median survival in phase 2 and 3 trials ranged from 15 to 24 months,5, 6 the median survival times published in the last decade have ranged from 36 to 40 months 7, 8…”