Efficacy of neoadjuvant cisplatin, adriblastin and cyclophosphamide (PAC) plus interleukin-2-based treatment versus PAC alone in patients with inoperable ovarian carcinoma

Ovarian carcinomas are the main cause of death from gynecological tumors in the western hemisphere and they are in fourth place in the USA and norther n Europe. Surgery is not recommended in advanced epithelial tumors as the m etastases in the various organs do not allow improvement in long-term survi val. Chemotherapy is the treatment of choice as A reduces tumor mass and me tastases, thus enabling cytoreductive surgery to be performed. it also prol ongs survival. We tested the efficacy of neoadjuvant cisplatin, adriblastin and cyclophosphamide (PAC) in the treatment of advanced inoperable ovarian carcinoma. Thirty-eight consecutive untreated patients aged between 56 and 75 years (mean age 62.7 +/- 4.8 years) were enrolled in the study Of the 3 8 patients, 19 received neoadjuvant treatment consisting of six PAC cycles repeated every 28 days (cisplatinum 100 mg/m2 i.v., adriblastin 50 mg/m2 i. v., cyclophosphamide 600 mg/m(2) i.v.) on day ? combined with interleukin ( IL)-2 (6,000,000 I.U s.c. on days 3-7 and days 75-19 after the chemotherapy session) while the remaining patients were treated with PAC alone. In 10 o f the 38 patients who underwent paracentesis, cytokine was administered int raperitoneally (single bolus 18,000, 000 I.U. after each session) and subcu taneously on days 15-19 after the chemotherapy session. Aii the patients in the study series completed the treatment. An objective response was obtain ed in ail patients treated with the protocol including IL-2 and in 10 of th e 79 treated with PAC alone. No response was seen in nine patients treated with PAC alone. Serum CA-125 levels were significantly decreased in 23 of t he 29 responders, 19 of wi,om were treated with the protocol including IL-2 (seven histoiogical type mucinous, 15 serous and seven endometrioid). in t he remaining responders and in the nine nonresponders, the marker decrease was not significant, The same parameter was not significant only for T-0 (b aseline) versus T-2 (after neoadjuvant therapy) in the group treated with P AC alone. The 29 responses were achieved in patients with various tumor sta ging (14 IIc, seven IIIa, three IIIb and five life), although better respon ses were obtained in patients with lower tumor staging. In conclusion, the association PAC plus IL-2 provided a greater number of responders and a lon ger overall survival than did chemotherapy alone (p < 0.001 and 0.0017 resp ectively); responders with more favorable disease characteristics (smaller stage and grading, better performance status, lower age, mucinous histotype and residual disease lesser than 1 cm) had a longer survival than the pati ents with less favorable characteristics; the adverse effects of our study series were not so severe as to provoke dropouts; serum Ca-125 levels signi ficantly decreased between T-0 and T-2 and between T-2 and T-3 (8 days afte r surgery) in the responders.