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.
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 <or= 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%).


CONCLUSIONS
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.
Pignata
Sandro
S
Medical Oncology B, National Cancer Institute, Naples, Italy. sandro.pignata@fondazionepascale.it
Scambia
Giovanni
G
Savarese
Antonella
A
Breda
Enrico
E
Scollo
Paolo
P
De Vivo
Rocco
R
Rossi
Emanuela
E
Gebbia
Vittorio
V
Natale
Donato
D
Del Gaizo
Filomena
F
Naglieri
Emanuele
E
Ferro
Antonella
A
Musso
Pietro
P
D'Arco
Alfonso Maria
AM
Sorio
Roberto
R
Pisano
Carmela
C
Di Maio
Massimo
M
Signoriello
Giuseppe
G
Annunziata
Annalisa
A
Perrone
Francesco
F
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000601:surgery; D010052:Ovariectomy; D010292:Paresthesia / Q000139:chemically induced; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced
D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016190:Carboplatin