Willy Mattsson

CVP—Remission—maintenance in stage I or II non‐Hodgkin's lymphomas Preliminary results of a randomized study

The effect of adjuvant combination chemotherapy when given to nonlaparotomized patients in remission after radiotherapy in stage I or II non‐Hodgkins lymphoma was studied in a prospective randomized multicenter study. Locally extended field radiotherapy was given to a target absorbed dose of 40 Gy in 20 fractions. Fifty‐five patients who were in complete remission 6 weeks after conclusion of radiotherapy were randomized to either no further therapy or to 9 cycles of CVP (cyclophosphamide +vincristine +prednisolone). The relapse‐free survival at 30 months was 41% for patients without and 86% for patients with adjuvant chemotherapy (p = 0.02). The survival was the same for both treatment arms, being 90% at 30 months. Fifteen patients have relapsed, 14 of them with extensions and 1 with a recurrence within the radiation target volume. Analysis of subgroups showed that adjuvant chemotherapy in the present series significantly prolonged the relapse‐free survival in diffuse histiocytic lymphoma.

A phase III trial comparing prednimustine (LEO 1031) to chlorambucil plus prednisolone in advanced breast cancer

Prednimustine is an ester of chlorambucil and prednisolone. The drug has had some activity in experimental as well as in human tumors, including breast cancer. The objective of the current study is to compare the clinical effectiveness and toxicity of prednimustine with its components of chlorambucil plus prednisolone, and to compare the clinical effectiveness and toxicity of a continuous treatment with an intermittent one. Two hundred and one patients with advanced breast cancer were randomized to the following treatments: I: prednimustine continuously; 40 mg/m2 d; II: prednimustine intermittently, 160 mg/m2 d 1 to 5, repeated every three weeks; and III: chlorambucil 8 mg/m2 d plus prednisolone 8 mg/m2 d, both given continuously. All treatments were given orally. One hundred and ninety five patients were evaluable for assessment of response to the treatments. The response rates were 21% in both of the prednimustine‐treated groups, whereas only 11% of the patients treated with chlorambucil and prednisolone responded. The duration of remission with continuous prednimustine was longer than with the other two treatment groups, but not significantly so. One hundred and ninety five patients were evaluable for assessment of hematologic toxicity. No differences were observed between the two prednimustine‐treated groups, whereas the group treated with chlorambucil plus prednisolone experienced a significantly higher degree of leukopenia and/or thrombopenia. Subjective toxicities, nausea, vomiting and psychical symptoms were only moderate in the three treatment groups, but significantly more pronounced in the group treated with intermittent prednimustine. Because of these promising results, prednimustine should be compared to other alkylating agents in patients with advanced breast cancer in randomized trials.

Prednimustine (NSC-134087, Leo 1031) treatment of lymphocytic and lymphocytic-histiocytic lymphomas.

Nineteen patients with advanced lymphocytic or lymphocytic‐histiocytic lyphomas were treated with Prednimustine (NSC‐134087, Leo 1031). The median induction dose was 25 mg/m2 a day by mouth (range 11‐42). Ten patients had previously received radiation or chemotherapy, or both. Four patients had a complete remission and eleven a partial remission. The median duration of remission was 12.5+ months for complete responders and 5 months for partial responders. Thirteen patients had a moderate myelosuppression. One patient had urticaria and pruritus and refused further treatment.

A phase II study of combined 5-fluorouracil and mitomycin C in advanced breast cancer

In a Phase II study, 50 patients with advanced breast cancer were treated with a combination of 5‐fluorouracil (1000 mg/m2 on days 1 and 2) and mitomycin C (6 mg/m2 on day 2) (FuMi regimen). The courses were repeated every third to sixth week. Although 35 patients had previously received combination chemotherapy and 40 patients had received endocrine treatment, objective responses were obtained in 29 patients (six complete, 23 partial). The survival was significantly correlated to the response (P < 0.001, log rank test) complete versus partial response, partial response versus no change, no change versus progressive disease. The regimen was well tolerated (19 of 50 experienced nausea). Thirteen patients had hematopoietic toxicity at the day of starting a new course and in six cases, the FuMi regimen had to be discontinued because of longlasting thrombocytopenia. Otherwise, no side‐effect of clinical importance was observed. The FuMi regimen is now compared with Adriamycin regimens and can be recommended for both first line chemotherapy and salvage chemotherapy.

Bleomycin‐mitomycin C in advanced carcinoma of the cervix: A third look

Thirty‐three patients with advanced cervical cancer (31 squamous cancer, two adenosquamous cancer) previously untreated with cytotoxic drugs, were treated with bleomycin, 5 mg daily, for seven days and mitomycin C, 10 mg, on day 8. This regimen was repeated four times at two‐week intervals. All but one patient had previously been treated with radiotherapy; 36% of the patients had an objective response (five complete remission (CR), median duration 12 months; seven partial remission (PR), median duration six months). Severe myelosuppression occurred in nine patients. One drug‐related death due to thrombocytopenia occurred. Three patients developed pulmonary fibrosis and one of them died of respiratory failure. The bleomycin‐mitomycin C regimen has a definite but clearly limited effect in advanced cancer of the uterine cervix.

Short-Term Intra-Arterial Mitomycin C in Hepatic Metastases

Short-term intra-arterial Mitomycin C treatment of hepatic metastases from various malignancies was performed in 24 evaluable patients. An objective regression was obtained in 12 patients. The median survival of responders was 11 months compared with 3 months in nonresponders. No complication of the technical procedure occurred and the treatment was well tolerated. The only side effect of clinical importance was thrombocytopenia, which occurred at a median dose of 45 mg of Mitomycin C.

Toxic epidermal injury following intraarterial adriamycin treatment.

Toxic epidermal injury was induced in the right forearm and thumb of a 74‐year‐old woman following two courses of 28 mg/m2 Adriamycin infused in the brachial artery with a three‐week interval. The toxic epidermal injury was treated with a wet dressing solution and a neomycin cream without corticoids; it healed in one month. Afterwards the woman received 22 courses of Adriamycin intravenously or intraarterially in 5.5 or 11 mg/m2 doses, but the toxic epidermal injury did not recur.

Combination chemotherapy in advanced postmenopausal mammary carcinoma. A comparison between VAC and VACM therapy.

A randomized trial comparing Vincristine, Adriamycin, Cyclophosphamide (VAC) with or without Methotrexate with citrovorum factor rescue (VACM) was performed in 64 patients with metastatic postmenopausal mammary carcinoma. Previous treatment of metastases, dominant site of metastases and performance condition were similar in the patients. No significant difference was found in the response rates (complete remission + partial remission; VAC 21/31, VACM 25/33), in the duration of the remissions or in the survivals. The duration of remission in CR was significantly longer than in PR. No serious side effects were observed. The VAC regimen is preferable, particularly with respect to the costs and the simple procedure of administration.

Chemotherapy of advanced transitional cell carcinoma of the renal pelvis: report of 3 cases treated with vinblastine and chloroethyl-cyclohexyl-nitrosourea.

Three patients with advanced transitional cell carcinoma of the renal pelvis were treated with 5 mg./m.2 body surface vinblastine intravenously weekly and 130 mg./m.2 chloroethyl-cyclohexyl-nitrosourea orally with 6-week intervals. One patient had a partial remission for 1.5 months and 2 had stationary disease for 6 and 2 months.

A phase II study of combined adriamycin, L-PAM, and methotrexate with citrovorum factor rescue in advanced ovarian carcinomas

In a phase II study of combined adriamycin, L-PAM, and methotrexate with citrovorum factor rescue, 14 of 15 patients with primary advanced or recurrent ovarian malignant tumors obtained an objective remission. In remission, all patients improved their quality of life. So far the median duration of remission is 5+ months for the complete responders and 7 months for the partial responders. Myelosuppression of varying severity occurred in 93 % of the courses. The regimen proved highly effective, although toxic in some advanced patients.