P. Alberto

A phase II study of oral VP-16-213 in non-seminomatous testicular cancer

Abstract In a disease-oriented phase II study, thirty-three patients with advanced non-seminomatous testicular cancer were treated with oral VP-16-213 175 mg/m 2 /day for three consecutive days repeated every week. All patients had previously received extensive chemotherapy and twenty patients also had prior radiotherapy, Of 30 evaluable patients, 6 experienced partial remission for a median duration of 3.5 months , whereas minor regression or stabilization of the disease was achieved in 7 patients for a median duration of 2.5 months . Leukopenia was dose-limiting and resulted in dose reduction or treatment delay in 55% of the scheduled courses. The definite antitumor activity of VP-16-213 in non-seminomatous testicular cancer warrants its incorporation into combination chemotherapy for this disease.

Phase II study of 5' deoxy 5 fluorouridine (doxifluridine) in advanced malignant melanoma

SummaryForty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m2 daily ×5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m2 in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts <1.5×109/l leukocytes or 50×109/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma.

Dianhydrogalactitol (NSC-132313): Phase II study in solid tumors

Abstract One hundred and sixty-two patients with advanced solid tumors were treated with oral dianhydrogalactitol 30 mg/m 2 daily for 10 days every 4–6 weeks . Dose limiting toxicity was hematopoietic. Eight objective responses were seen in 136 evaluable cases. Patients with gastro-intestinal cancer (213 gastric, 13 pancreatic, 223 colorectal) showed objective regressions lasting 1–12 + months . Short lasting partial remissions occurred in 220 lung epidermoid and 118 breast carcinomas. Dianhydrogalactitol has limited chemotherapeutic activity against adult solid tumors but deserves further trial in gastro-intestinal malignancies.

Initial clinical experience with a simultaneous combination of 2,4-diamino-5(3′,4′-dichlorophenyl)-6-methylpyrimidine (DDMP) with folinic acid

SummaryDDMP, a diaminopyrimidine folate antagonist, was given to 26 tumor patients in a dosage of 50 mg/m2 per week orally, simultaneously with 3 mg CF i.m. or i.v. The CF dose was increased to 30 mg in patients showing evidence of toxicity, and withdrawn in the absence of toxicity. The dose-limiting toxicity was seen in myelosuppression, particularly thrombopenia and skin rashes. At the 3 mg CF level, 18 out of 26 patients developed toxicity. No toxicity was seen at the 30 mg CF level in 11 patients. After cessation of CF, toxicity occurred in five out of seven patients. After the onset of toxicity, CF was added as a delayed rescue, in a dosage of 15 mg every 8 h or 30–60 mg daily. One patient died of sepsis with agranulocytosis. All other patients recovered from myelosuppression within 1 or 2 weeks. Objective responses were observed in seven patients, four of the ten with epidermoid cancer of the head and neck, two out of eight with epidermoid cancer of the lung, and one out of three with melanoma.

Rapidly alternating combination of cisplatinbased chemotherapy and hyperfractionated accelerated radiotherapy in split course for stage IIIA and stage IIIB non-small cell lung cancer: Results of a phase I-II study by the GOTHA group

Abstract The prognosis of stage III non-small cell lung cancer (NSCLC) can be improved by a combination of radiotherapy (RT) and chemotherapy (CT). In this study, the GOTHA group evaluated the feasibility, tolerance, tumour response, pattern of failure and effect on survival of a combination alternating accelerated hyperfractionated (AH) RT and CT in patients with tumour stage III NSCLC. 65 patients received 3 cycles of cisplatin 60 mg/m2 and mitomycin C 8 mg/m2 on day 1, and vindesin 3 mg/m2 on days 1 and 8 in weeks 1–2, 5–6 and 9–10, alternating with AHRT, 2 daily 1.5 Gy fractions, 5 days/week, in weeks 2–3 (30 Gy) and weeks 6–7 (33 Gy). The dose actually delivered was >98% for RT, and 85–100% for CT. Mean duration before last CT cycle was 9.5 weeks. Toxic effects were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopecia and peripheral neuropathy. 1 patient died of bronchial haemorrhage at the end of RT. 1 of 5 patients, who underwent secondary pulmonary resections, died of acute respiratory distress syndrome. Evaluation of tumour response was hampered by lung condensations in radiation fields. Some long-term survivors had an initial tumour response assessed as partial response or no change. First failures were more frequent outside (34) than within (21) radiation fields. The median survival was 15.7 months and the 5 year survival rate was 15% (95% CI = 6–26%). 1 patient died of bladder cancer and another of myocardial infarction. Alternating CT and AHRT, as used in this study, were well tolerated and allowed full dose delivery within less than 12 weeks. Initial response was not predictive of survival. The survival curve is encouraging and the 5 year survival is superior to the 5% generally observed with conventionally fractionated radiotherapy.

Phase II study of amsacrine in solid tumors: a report of the EORTC Early Clinical Trial-Group.

A total of 239 patients with advanced solid tumors were treated in this phase II trial. Amsacrine was administered as a single i.v. dose of 120 mg/m2 repeated at 21-day intervals. The initial dose was reduced to 90 mg/m2 in the case of extensive prior therapy. Some antitumor activity was detected in head and neck cancer but the drug appears to lack significant efficacy in epidermoid lung cancer as well as in carcinoma of the breast, melanoma, renal cell cancer, colorectal cancer and non-seminomatous testicular cancer. Leukopenia was the major toxic effect encountered in this trial and was similar at 90 and 120 mg/m2.

Phase II study of anhydro-ara-5-fluorocytidine in adenocarcinoma of gastrointestinal tract, epidermoid carcinoma of lung, head and neck, breast carcinoma and small cell anaplastic carcinoma of lung. A study report of the E.O.R.T.C. early clinical trial cooperative group.

Abstract AAFC is a fluorinaled anhydride analog of cytosine arabinoside, partially hydrolysed in vivo into ara-FC and ara-FU. Antitumor activity has been observed during phase I studies in acute leukemia and solid tumors. A hundred and sixty six patients with advanced tumors belonging to selected histological types received AAFC, 15–20 mg/kg daily × 5 q3w, or 33–40 mg/kg weekly i.v. during 3 weeks or longer. One hundred and thirty-two observations were fully evaluable including 67 without and 65 with prior chemotherapy. Responses were observed in adenocarcinoma of stomach ( 7 14 ), pancreas ( 2 3 ) and colon and rectum ( 2 32 ), epidermoid carcinoma of head and neck ( 4 30 ), breast carcinoma ( 1 17 ) and small cell carcinoma of lung ( 1 9 ), but not in epidermoid carcinoma of lung ( 0 27 ). Both treatment schedules were active. There were 8 67 responders among not pretreated and 9 65 among pretreated patients. Toxicity was more pronounced after daily × 5 application. The limiting toxicity consisted in anemia, leucopenia, thrombopenia, nausea and vomiting. Parotid pain or postural hypotension were not observed.

Chemotherapy of inoperable lung cancer

Abstract Primary cancer of the lung is the most frequent malignant tumor in males and its frequency is increasing rapidly in females. The failure rate after curative treatment including surgery and/or radiotherapy is about 80%. Since a large proportion of lung tumors are inoperable at the time of diagnosis, chemotherapy is an important palliative treatment. Single drug chemotherapy is relatively ineffective; combination chemotherapy reaches a 50 to 90% response rate in small cell carcinomas while the failure rate is 50% or more in adenocarcinoma and large cell anaplastic carcinoma. Results presently obtained with squamous cell carcinoma are generally disappointing, although recently published preliminary series suggest some improvement with the use of combinations of newer agents.