J. H. Mulder

Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC soft tissue and bone sarcoma group☆

The objective of this randomized phase II/phase III study was to investigate the efficacy and toxicity of equimolar doses of adriamycin (ADM) and 4-epiadriamycin (EPI) in patients with locally advanced and/or metastatic soft tissue sarcoma. Doses of ADM and EPI were 75 mg/m2 given as an i.v. bolus injection every 3 weeks. Two hundred and ten patients were entered into the study by 18 institutions. Twenty-eight patients were ineligible and 15 were non-evaluable, leaving 167 evaluable patients. The two treatment groups were well balanced for sex, performance status, age, prior radiotherapy, extent and site of disease. Rates of response were similar, 25% in the ADM group compared to 18% in the EPI group (P = 0.33), and there were no significant differences between the ADM and EPI groups with respect to median duration of response (45 weeks vs. 77 weeks, P = 0.08), time to progression (15 weeks vs. 12 weeks, P = 0.945), and median survival (41 weeks vs. 48 weeks, P = 0.363). Myelotoxicity as shown by leucopenia was significantly more pronounced in the ADM treated patients (P = 0.002). Other toxicities such as alopecia and nausea/vomiting were also more severe in the ADM group (P = 0.02 and 0.06, respectively). In conclusion, the use of equimolar doses of ADM and EPI in advanced soft tissue sarcoma produced response rates which did not differ significantly and were only slightly in favour of ADM. However, this was achieved at the expense of higher toxicity.

Carminomycin vs adriamycin in advanced soft tissue sarcomas: an EORTC randomised phase II study.

Eighty-three patients with advanced soft tissue sarcoma who had received no prior chemotherapy entered a randomised phase II study comparing carminomycin (CMM) 20 mg/m2 with adriamycin (ADM) 75 mg/m2, both administered i.v. bolus every 3 weeks. Six patients were ineligible and response could not be evaluated in 6 additional patients. Thirty-eight evaluable patients received ADM and 33 received CMM. There was one complete response to ADM and 10 partial responses, an overall response rate of 29%. CMM showed significantly (P = 0.01) lower antitumour activity--one partial response (3%). Stabilisation of disease was similar in both arms (47 and 45%), but fewer patients progressed on ADM (24 compared to 52%). Durations of response dating from the start of chemotherapy were 5 months for complete remission on ADM, a median of 7 months (range 4-17) for partial response on ADM and 14 months for the one partial remission on CMM. Although the median time to progression for all patients receiving CMM (2 months) was significantly (P = 0.001) shorter than for those receiving ADM (5 months), patients on ADM had only a marginally significant longer duration of survival (P = 0.06) than the patients receiving CMM. A leucocyte nadir less than 2.0 X 10(9)/l occurred in 38% of patients receiving ADM and 43% receiving CMM. Anaemia and thrombocytopoenia were uncommon. Other toxicities such as nausea, vomiting, anorexia and alopecia were more severe in the ADM group. There was one infective death secondary to leucopoenia in the ADM arm, and one patient who had received 109 mg/m2 CMM + 255 mg/m2 ADM developed progressively fatal cardiomyopathy.

Combination chemotherapy with cisplatin and VM-26 in advanced transitional cell carcinoma of the bladder☆

Abstract Forty-one evaluable patients with bidimensionally measurable metastases of transitional cell carcinoma of the bladder were treated with cisplatin 70 mg/m 2 i.v. on day 1 and VM-26 100 mg/m 2 i.v. on days 1 and 2, every 3 weeks . Response was evaluated after 2 treatment cycles. Complete response (CR) was achieved in 4 patients (10%) and partial response (PR) in 17 (41%). The median response duration was 6 months . In this group of previously untreated patients the combination of cisplatin and VM-26 did not appear to yield better response rates than would be expected from cisplain alone.

Cisplatin and vindesine combination chemotherapy in advanced malignant melanoma: an EORTC phase II study☆

Sixty-one evaluable patients with measurable advanced malignant melanoma received 4-week courses of a combination of cisplatin 100 mg/m2 as a 24-hr i.v. infusion on day 1 and vindesine 3 mg/m2 as an i.v. bolus on days 1, 8, 15 for two courses and every other week thereafter. Two patients achieved complete response for 46 and 81+ weeks respectively, eleven patients achieved partial response for a median of 17 weeks (range 8-26) and three patients had no change for 24 weeks or more. The overall response rate of 21% did not seem to be affected by prior chemotherapy or site of indicator lesions, soft tissue vs visceral. Myelosuppression, consisting essentially of leucopenia, required dose schedule modifications in 41% of the first two courses and 12% of the remaining courses, but never produced major complications. Non-hematologic toxic effects were prominent, especially nausea and vomiting, which were universal. Alopecia was seen in 71% of the patients, neuromuscular manifestations in 39%, diarrhea in 30%, renal impairment in 25%, mucositis in 12%, ototoxicity in 7% and phlebitis in 3%. These results do not suggest striking additive or synergistic antitumor activity of cisplatin and vindesine in advanced malignant melanoma, at least with the method of drug administration selected for this trial.

N-(Phosphonacetyl)-l-aspartate (PALA) in advanced malignant melanoma: A phase II trial of the EORTC malignant melanoma cooperative group

Thirty-nine patients with measurable advanced malignant melanoma were entered in a phase II trial with PALA. Among the 36 evaluable patients there were 18 men and 18 women, with a median age of 53 yr (29-73) and a median performance status (Karnofsky) of 100 (50-100). Indicator lesion consisted essentially of soft tissue lesions (29 patients) and/or lung metastases (9 patients). Only three patients had received prior chemotherapy. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-8) were administered. Partial response (greater than 50%) was obtained in 4 patients for 6-17 weeks. Eight patients had stable disease after 3 courses of PALA and 24 had progressive disease. Toxic effects were generally mild to moderate and mainly included cutaneous toxicity, nausea and vomiting, stomatitis, and diarrhea. Myelosuppression was rare and negligible. It is concluded that PALA given at the dose schedule selected for this trial is fairly well tolerated and has borderline antitumor activity in good-risk patients with advanced malignant melanoma.

Mitoxantrone in advanced bladder carcinoma. A phase II study of the EORTC genito-urinary tract cancer cooperative group

Mitoxantrone at a dose of 12 mg/m2 i.v. q 3 weeks failed to produce a response in 28 adequately treated patients with measurable advanced bladder cancer. The side-effects observed in this group of patients with a good performance status were generally mild. On the basis of this negative result the use of mitoxantrone in this disease cannot be recommended.

Chemotherapy in Advanced Soft Tissue Sarcoma — The EORTC Experience

The Soft Tissue and Bone Sarcoma Group (STBSG) is one of the 17 clinical cooperative groups of the European Organization for Research and Treatment of Cancer (EORTC). It was constituted in 1975 and increased from nine full members in 1976 to 21 full and 11 probational members from nine European countries by 1987.

Combination Chemotherapy with Cisplatin and VM-26 In Advanced Transitional Cell Carcinoma of the Bladder, An EORTC Study

Forty-one evaluable patients with bidimensionally measurable metastases of transitional cell carcinoma of the bladder were treated with cisplatin 70 mg/m2 i.v. on day 1 and VM-26 100 mg/m2 i.v. on days 1 and 2, every 3 weeks. Response was evaluated after 2 treatment cycles. Complete response (CR) was achieved in 4 patients (10%) and partial response (PR) in 17 (41%). The median response duration was 6 months. In this group of previously untreated patients the combination of cisplatin and VM-26 did not appear to yield better response rates than would be expected from cisplatin alone.