Open Access Highly Accessed 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, Francesco Perrone16 and the MITO Investigators (see appendix)

Author Affiliations

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

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

Published: 1 August 2006



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.


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.


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%).


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.