Pergamon Eumpcm1JdofCancrrVol. 31A, No. 12, pp. 1987-1992,1995 Ekvier Science Ltd RintedinGrcatBtitait~ 095~8049/95 $9.50+0.00 Original Paper Very High-dose Chemotherapy with Autologous Peripheral Stem Cell Support in Advanced Ovarian Cancer P. Benedetti-Panici,l S. Greggi,’ G. Scambia,’ M.G. Salerno,’ G. Baiocchi,’ G. Laurelli,’ G. Menichella,2 L. Pierelli,2 M.L. Foddai,2 R. Serafki,2 B. Bizzi2 and S. Mancusol ‘Department of Gy naecology and 2Department of Haematology, Catholic University, Largo A. Gemelli, 8,00168 Rome, Italy 20 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA patients with stage III-IV ovarian cancer were submitted to induction chemotherapy (ICT) (40 mg/m* cisplatin, days l-4; 1.5 g/m* cyclophosphamide, day 4; every 4 weeks for 2 cycles) followed by intensified CT (100 mg/m* cisplatin, day 1; 650 mg/m* etoposide, day 2; 1.8 g/m* carboplatin by 24 h infusion, day 3). Haematological support consisted of autologous peripheral stem cells (APSC) and bone marrow (ABM) transplant (T) in 16 and 4 patients, respectively. All patients were evaluable for toxicity and 19 for pathological response (PR), one patient dying of systemic mycosis after ABMT. Severe (grade M) non-haematological toxic effects were gastrointestinal (lOO%), neurological (10%) and hepatic (10%). PR was observed in 84% of patients (complete response 37%, partial response with microscopic residual disease 26%, partial response with macroscopic residual disease 21%). Five year overall survival was 60% and progression-free survival was 51% with 9 patients still disease-free (DFS). APSCT significantly reduced the duration of aplasia compared with ABMT, and toxicity was acceptable in those patients undergoing APSCT. The prolonged DFS in patients showing PCR suggests that this new approach may have a therapeutic impact. Key words: ovarian carcinoma, high-dose chemotherapy, autologous peripheral stem cell transplantation EurJ Cancer, Vol. 31A, No. 12, pp. 1987-1992,1995 INTRODUCTION OVARIAN CANCER is the fifth leading cause of cancer death in women, and the majority of patients have advanced stage disease at the time of diagnosis. Although clinical responses can be achieved in over half of all patients with current platinum- based chemotherapy regimens, only a minority enjoy prolonged disease-free survival (DFS). In particular, median survival is longer than 3 years only for patients who have residual tumour less than 0.5 cm after primary surgery. Clearly, there is an urgent need for innovative strategies to improve prognosis, especially in patients with larger postoperative residual disease. In recent years, the concept of the dose-response relationship has formed an integral part of the principle of treatment of haematological and solid tumours. In fact, virtually all anticancer agents have shown both therapeutic and toxic endpoints [l]. With regard to ovarian cancer, high-dose cisplatin has proved to be effective in some patients failing standard-dose regimens and response rates seem to be increased by dose escalation of platinum in phase I-II studies [2-6]. Moreoever, preliminary Correspondence to S . Mancuso. Revised 28 Mar. 1995; accepted 15 Jun. 1995. data on the use of combinations further suggest that dose intensification may produce superior results [5, 7-91. Therefore, the use of platinum dose intensification regimens with haematological support has been suggested in previously untreated selected patients [lo, 111. In particular, according to our previous results with high-dose cisplatin [12], dose intensification programmes seem to be worthwhile in patients with minimal macroscopic residual disease rather than in those with large tumour burdens [13]. Unfortunately, prohibitive peripheral neurotoxicity occurs when cisplatin is escalated to very high doses [12]. Carboplatin has shown similar activity in ovarian carcinoma to cisplatin [ 141, but it causes less nausea and vomiting, neurotoxicity and nephrotoxicity, with the dose- limiting toxicity being myelosuppression, in particular throm- bocytopenia. Combination cisplatin and carboplatin therapy may permit the administration of higher doses of platinum than a single analogue, as these agents have non-overlapping toxicities [15, 161. Moreover, the lack of non-haematological toxicity makes carboplatin a potentially useful drug in a high-dose chemotherapy setting, when recovery from myelosuppression can be accomplished by use of adequate haematological support [ 17-191. Among the other alkylating agents, etoposide may be 1987