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Topotecan Compared With No Therapy After Response to Surgery and Carboplatin/Paclitaxel in Patients With Ovarian Cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) Randomized Study

From the Dipartimento di Endocrinologia e Oncologia Sperimentale e Clinica, Università Federico II di Napoli; Oncologia Medica, Ospedale Cardarelli; Oncologia Medica C, Oncologia Medica B, Ginecologia Oncologica, and Unità Operativa Sperimentazioni Cliniche, Istituto Nazionale Tumori di Napoli; Cattedra di Statistica Medica, Seconda Università di Napoli, Napoli; Istituto di Ginecologia ed Ostetricia, Policlinico Universitario Gemelli; Oncologia Medica, Azienda Ospedaliera S. Filippo Neri, Roma; Ginecologia II and I Clinica Ostetrica Ginecologica, Università di Bari; Oncologia Medica e Sperimentale, Istituto Nazionale Tumori di Bari, Bari; Clinica Malzoni, Avellino; Oncologia Medica, Ospedale Mariano Santo, Cosenza; Oncologia Medica, Azienda Ospedaliera S. Carlo, Potenza; Oncologia Medica, Ospedale Fatebenefratelli, Benevento; Oncologia Medica, Policlinico Giaccone, Palermo; and Ginecologia, Ospedale S Anna, Torino, Italy

Address reprint requests to Sandro Pignata, MD, PhD, Istituto Nazionale Tumori, via M Semmola, 80131–Napoli, Italy; e-mail: sandro.pignata{at}fondazionepascale.it

PURPOSE: Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown.

PATIENTS AND METHODS: To investigate whether topotecan (1.5 mg/m² on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m² administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP.

RESULTS: Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P = .83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP.

CONCLUSION: The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

The Unità Operativa Sperimentazioni Cliniche, Istituto Nazionale Tumori di Napoli, is supported by Associazione Italiana per la Ricerca sul Cancro and Clinical Trials Promoting Group.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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