A. Kobierska

The Effect of Debulking Surgery after Induction Chemotherapy on the Prognosis in Advanced Epithelial Ovarian Cancer

BACKGROUND Although the value of primary cytoreductive surgery for epithelial ovarian cancer is beyond doubt, the value of debulking surgery after induction chemotherapy has not yet been defined. In this randomized study we investigated the effect on survival of debulking surgery. METHODS Eligible patients had residual lesions measuring more than 1 cm in diameter after primary surgery. After three cycles of cyclophosphamide and cisplatin, these patients were randomly assigned to undergo either debulking surgery or no surgery, followed by further cycles of cyclophosphamide and cisplatin. The study end points were progression-free and overall survival. At surgery 65 percent of the patients had lesions measuring more than 1 cm. In 45 percent of this group, the lesions were reduced surgically to less than 1 cm. RESULTS Of the 319 patients who underwent randomization, 278 could be evaluated (140 patients who underwent surgery and 138 patients who did not). Progression-free and overall survival were both significantly longer in the group that underwent surgery (P = 0.01). The difference in median survival was six months. The survival rate at two years was 56 percent for the group that underwent surgery and 46 percent for the group that did not. In the multivariate analysis, debulking surgery was an independent prognostic factor (P = 0.012). Overall, after adjustment for all other prognostic factors, surgery reduced the risk of death by 33 percent (95 percent confidence interval, 10 to 50 percent; P = 0.008). Surgery was not associated with death or severe morbidity. CONCLUSIONS Debulking surgery significantly lengthened progression-free and overall survival. The risk of death was reduced by one third, after adjustment for a variety of prognostic factors.

The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer

BACKGROUND Although the value of primary cytoreductive surgery for epithelial ovarian cancer is beyond doubt, the value of debulking surgery after induction chemotherapy has not yet been defined. In this randomized study we investigated the effect on survival of debulking surgery. METHODS Eligible patients had residual lesions measuring more than 1 cm in diameter after primary surgery. After three cycles of cyclophosphamide and cisplatin, these patients were randomly assigned to undergo either debulking surgery or no surgery, followed by further cycles of cyclophosphamide and cisplatin. The study end points were progression-free and overall survival. At surgery 65 percent of the patients had lesions measuring more than 1 cm. In 45 percent of this group, the lesions were reduced surgically to less than 1 cm. RESULTS Of the 319 patients who underwent randomization, 278 could be evaluated (140 patients who underwent surgery and 138 patients who did not). Progression-free and overall survival were both significantly longer in the group that underwent surgery (P = 0.01). The difference in median survival was six months. The survival rate at two years was 56 percent for the group that underwent surgery and 46 percent for the group that did not. In the multivariate analysis, debulking surgery was an independent prognostic factor (P = 0.012). Overall, after adjustment for all other prognostic factors, surgery reduced the risk of death by 33 percent (95 percent confidence interval, 10 to 50 percent; P = 0.008). Surgery was not associated with death or severe morbidity. CONCLUSIONS Debulking surgery significantly lengthened progression-free and overall survival. The risk of death was reduced by one third, after adjustment for a variety of prognostic factors.

Phase I Study of High-Dose Epirubicin in Platinum-Pretreated Patients with Ovarian Carcinoma

Background: In vitro data demonstrated a dose-response relationship for doxorubicin in ovarian cancer (OC) cell lines. However, this dose-response question for doxorubicin was never carefully addressed in OC patients. These data and the more favorable toxicity profile of the anthracycline analogue epirubicin prompted us to study high-dose epirubicin (HDE) in relapsed OC patients. Patients and Methods: This phase I study included 19 OC patients with measurable or evaluable disease and no more than one prior (cisplatin-containing) chemotherapy regimen. Dose escalation was not allowed in individual patients. Epirubicin was administered by rapid intravenous infusion (<5 min) once every 3 weeks and studied at the following dose levels: 120, 135, 150, 180 and 200 mg/m2 (at least 3 patients per dose level). None of the patients received hematopoietic growth factors. We defined the maximum tolerated dose (MTD) as the dose at which we observed WHO grade 4 hematologic toxicity in ≥50% and/or WHO grade 3 nonhematologic toxicity in ≥30% of the patients. Results: The MTD was 200 mg/m2, with DLT being both hematologic (leukopenia and/or thrombocytopenia) and nonhematologic (mucositis). Objective responses were observed in 6 patients (response rate 32%), 3 of them occurring in 10 patients with primary platinum resistance. Conclusions: HDE is tolerable and has activity in second-line after cisplatin-based chemotherapy in OC patients. The recommended dose for phase II trials in such patients is 150 mg/m2, with escalation to 180 mg/m2 if toxicity permits.

Phase II study of fotemustine in patients with advanced ovarian carcinoma. A trial of the EORTC Gynecological Cancer Group

30 patients with advanced ovarian cancer, all platinum pretreated, were treated with an induction cycle of fotemustine. Maintenance therapy was given to 6 patients. No objective response was observed among the 21 evaluable patients. The main toxicities were gastrointestinal, with grade 3 nausea and vomiting reported in 40% of the patients, and haematological, with grade 4 leucopenia reported in 2 patients and grade 4 thrombocytopenia in 5 patients. Therefore, no role has been demonstrated in our cohort for the use of fotemustine, a nitrosourea, in pretreated ovarian cancer.

EORTC-GCCG Phase-II-Studien beim metastasierten Karzinom der Cervix uteri

Obwohl die Mortalitat beim Zervixkarzinom durch die weit verbreiteten zytologischen Screeningprogramme deutlich reduziert wurde, haben sich die stadienspezifischen Uberlebensraten wahrend der vergangenen 20 Jahre nicht signifikant verandert. 40–50% der wegen eines invasiven Zervixkarzinoms behandelten Patientinnen erleiden irgendwann ein Rezidiv. Wenn solche Patientinnen einmal Fernmetastasen entwickelt haben, ist die Uberlebenszeit i. allg. kurzer als 18 Monate [2, 3]. Aus diesem Grund erscheint eine systemische Behandlung theoretisch als der einzig mogliche kurative Behandlungsansatz bei Patientinnen mit einem Zervixkarzinom in fortgeschrittenen Stadien.