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In a planned prospective study 39 consecutive patients with stage III ovarian cancer have been admitted in two years. All patients have received initial extensive surgery followed on as out patients basis by 5 courses of A-Cy chemotherapy and by a second operation and further non cross resistant chemotherapy with Platinum, Hexamethyl-Melamine, Polymelphalan; 24 have been found pathologically free of disease at second surgery, and 34/39 are clinically free of disease while reporting. These data, exactly collected and evaluated are consistent with our (previously reported) empyrical observation that adjuvant surgery interspersed with courses of aggressive chemotherapy may render free of disease the majority of patients, prolong survival, and possibly cure a portion of this population.

From September 1975 to December 1981, 63 consecutive untreated patients with multiple myeloma received the Lee M-2 protocol. We used the same drugs (melphalan, cyclophosphamide, vincristine, BCNU and prednisone) but employed the lowest suggested doses and recycled earlier, i.e. after 21-28 days. Thirty-five patients (62.5%) were in stage III, 16 (28.6%) in stage II and 5 (8.9%) in stage I. An objective response (reduction in paraprotein production rate greater than 50%) was obtained in 44 out of 56 cases (78%); 32 (57%) had a reduction greater than 75%. The median duration of response was 21.5 months. In responding patients the treatment was stopped after 1 yr and resumed only at relapse. Twenty-two out of 25 retreated patients are now evaluable. Eighteen of them (82%) responded again; in retreatment the degree of response was lower, but the duration of second response was only slightly lower than the first response (15.7 vs 21.5 months, NS). Of 7 patients receiving a third M-2 reinduction 4 responded again. The median survival for all the patients is 51 months. The high rate of second response to the M-2 regimen after an unmaintained remission brings into question the value of continuous therapy in responsive multiple myeloma.

Forty-four previously untreated patients with advanced inoperable and/or disseminated gastric carcinoma were given an i.v. combination (FAM2) chemotherapy of 5-fluorouracil, 400 mg/m2 on days 1, 2 and 3, and 21, 22 and 23; adriamycin, 40 mg/m2 on days 2 and 22; and mitomycin C, 10 mg/m2 on day 1, with a recycle on day 42 (1 cycle = 41 days). Forty patients have completed 2 cycles and are evaluable (median number of cycles 5; range 3 to 8): 26 of these achieved a partial remission, with a response rate of 65%; 4 (10%) gained a stable situation for 3 to 6 months, and 10 (25%) showed progression of disease. Median duration of partial remissions was 10 months, and median survival was 15 months for responders and 5 months for nonresponders. A fall in WBC (less than 2500/microliter) occurred in 7% and of platelets (less than 80,000/microliter) in 4.5%. Total alopecia occurred in 20 of 40 patients and nausea and or weakness were common findings. No drug-related infection, bleeding or death was observed. Patients with advanced gastric carcinoma can derive useful palliation from FAM2 chemotherapy.

Fourteen patients with diffuse tumors of the liver were treated with temporary occlusion of the hepatic artery (HA) by an external tourniquet followed by infusion and systemic chemotherapy. Three patients had primary neoplasms (one hepatocarcinoma and two cholangiocarcinomas) and eleven had metastatic disease (nine from carcinoma of the colon and rectum, one from retroperitoneal liposarcoma, and one from pulmonary small cell cancer). Infusion chemotherapy in all patients was based on 5-FU, Mitomycin and Vincristine. Systemic chemotherapy was FIVB in metastatic carcinoma and Adriamycin in primary liver tumors. All patients showed improvement of the performance status according to the Karnofsky Index. Objective response (OR) was present in 54% of cases. At present, median survival time in 12.5 months. Aggressive treatment combining hepatic ischemia with infusion and systemic polychemotherapy seems to provide an effective method of palliation in diffuse tumors of the liver. Delayed occlusion by an external tourniquet appears safer than intraoperative ligation of the HA.

Twenty-one patients with alkylator-resistant plasmacell neoplasms were treated with Peptichemio (PTC) at a dose of 40 mg/m2 for 3 days every 3 weeks or, in the case of persistent leukopenia and/or thrombocytopenia, at the single dose of 70 mg/m2 every 2-3 weeks according to haematological recovery. Seventeen patients, 10 with multiple myeloma and seven with extramedullary plasmacytoma (EMP), were fully evaluable. Six of 17 patients (35%) responded: three of seven EMP patients had a complete remission and 3 of 10 multiple myeloma patients had an objective response greater than 50%. The median duration of response was 8.5 months. An EMP patient obtained a complete response lasting for 16 months. The most frequent toxic effect were phlebosclerosis, occurring in all the patients, and myelosuppression, which was severe in only one case. PTC appears to be an active drug in patients with plasmacell neoplasms even if resistant to alkylating agents.

Forty patients with advanced squamous cell carcinoma of the esophagus were treated with a combination of cisplatin, 5-FU (by continuous 5-day infusion), and allopurinol; 37 are evaluable for response. Thirteen remissions (35%) were obtained, including three complete and ten partial, with a median duration of 9 months. After chemotherapy, seven responding patients underwent a surgical procedure, which was radical in four. The most frequent side effects were nausea and vomiting. This regimen is effective and can be included in a multimodality approach.

From January 1978 to October 1982, 47 patients with histological diagnosis of epithelial cancer of the ovary received peptichemio (PTC) at a dose of 70 mg/m2 (maximum, 120 mg total) every 15 days. Forty-two patients are now evaluable: 27 with stage III and 15 with stage IV disease. All patients but four with stage IV disease had been pretreated and had received at least one drug combination (median, three drugs per patient, including alkylating agents). Before the administration of PTC, the tumor extension in the abdomen was carefully assessed in all patients: ten patients had residual tumor less than 2 cm in diameter, while 32 patients had tumor greater than 2 cm in diameter. Objective responses were obtained in ten patients (23.8%): six complete remissions and one partial remission were observed in stage III patients and one complete remission and two partial remissions were observed in stage IV patients. Of the ten responding patients, eight had tumors less than 2 cm in diameter before receiving PTC. The median duration of response was 16 months. The most frequent side effects were myelosuppression and phlebosclerosis. Bone marrow depression was a common finding after the third course in heavily pretreated patients. Accordingly, in these patients a schedule interval of 3 weeks should be more appropriate. Since most of the responders were in the "small tumor" category, PTC appears to be an active drug in patients with ovarian cancer having small tumors (less than 2 cm). On the other hand, the response rate in a nonselected population of patients remains to be clearly defined with further studies.