Research article

Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial

Sandro Pignata¹ , Giovanni Scambia² , Antonella Savarese³ , Enrico Breda⁴ , Paolo Scollo⁵ , Rocco De Vivo⁶ , Emanuela Rossi⁷ , Vittorio Gebbia⁸ , Donato Natale⁹ , Filomena Del Gaizo¹⁰ , Emanuele Naglieri¹¹ , Antonella Ferro¹² , Pietro Musso¹³ , Alfonso Maria D'Arco¹⁴ , Roberto Sorio¹⁵ , Carmela Pisano¹ , Massimo Di Maio¹⁶ , Giuseppe Signoriello¹⁷ , Annalisa Annunziata¹⁷ and Francesco Perrone¹⁶ for the MITO Investigators (see appendix)

¹  Medical Oncology B, National Cancer Institute, Naples, Italy

²  Gynecologic Oncology Unit, Catholic University of the Sacred Heart, Rome, Italy

³  Medical Oncology A, Regina Elena Institute, Rome, Italy

⁴  Medical Oncology, Fatebenefratelli Hospital, Rome, Italy

⁵  Gynecology, Cannizzaro Hospital, Catania, Italy

⁶  Medical Oncology, S. Bortolo Hospital, Vicenza, Italy

⁷  Medical Oncology C, National Cancer Institute, Naples, Italy

⁸  Medical Oncology I, La Maddalena Clinic, Palermo, Italy

⁹  Medical Oncology, S. Massimo Hospital, Penne (PE), Italy

¹⁰  Medical Oncology, S. Giuseppe Moscati Hospital, Avellino, Italy

¹¹  Medical and Experimental Oncology Unit, Oncology Institute, Bari, Italy

¹²  Medical Oncology, S. Chiara Hospital, Trento, Italy

¹³  Gynecologic Oncology, M. Ascoli Hospital, Palermo, Italy

¹⁴  Medical Oncology, Umberto I Civil Hospital, Nocera Inferiore (SA), Italy

¹⁵  Medical Oncology C, National Cancer Institute – Centro di Riferimento Oncologico, Aviano (PN), Italy

¹⁶  Clinical Trials Unit, National Cancer Institute, Naples, Italy

¹⁷  Department of Medicine and Public health, Second University of Naples, Italy

author email corresponding author email

BMC Cancer 2006, 6:202doi:10.1186/1471-2407-6-202

Published:	1 August 2006

Abstract

Background

The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned.

Methods

Patients with ovarian cancer (stage Ic-IV), aged < 75 years, ECOG performance status ≤ 2, were randomized to carboplatin AUC 5 plus paclitaxel 175 mg/m², every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30 mg/m², every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded according to the NCI-CTC version 2.0.

Results

The pre-planned safety analysis was performed in July 2004. Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was 60 years (range 34–75). Forty-three patients (86%) completed 6 cycles. Two thirds of the patients had at least one cycle delayed due to toxicity, but 63% of the cycles were administered on time. In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity. No delay due to palmar-plantar erythrodysesthesia (PPE) was recorded. No toxic death was recorded. Reported hematological toxicities were: grade (G) 3 anemia 16%, G3/G4 neutropenia 36% and 10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non-haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%, liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%, G2 2%, G3 2%).

Conclusion

This safety analysis shows that the adopted schedule of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is feasible as first line treatment in ovarian cancer patients, although 37% of the cycles were delayed due to haematological toxicity. Toxicities that are common with standard combination of carboplatin plus paclitaxel (neurotoxicity and hair loss) are infrequent with this experimental schedule, and skin toxicity appears manageable.