A phase II study of mitomycin C, vindesine and cisplatin combined with alpha interferon in advanced non-small cell lung cancer.

AIMS AND BACKGROUND: MVP chemotherapy (mitomycin C, vindesine or vinblastine, cisplatin) is one of the most commonly used regimens for advanced non-small cell lung cancer (NSLCLC). Experimental data suggest a synergistic cytotoxic activity of alpha-interferon (alpha-IFN) when combined with cisplatin, mitomycin C and vinca alkaloids. In an effort to improve MVP chemotherapy activity, we have combined this regimen with alpha-IFN. PATIENTS AND METHODS: Thirty-five patients with advanced NSCLC (19 stage IV) were treated with the MVP regimen (mitomycin C, 8 mg/m2; vindesine, 3 mg/m2, cisplatin, 75 mg/m2, all on day 1) plus alpha-2a-IFN, 3x10(6) U from day 1 to 7. The cycles were repeated every 28 days. RESULTS: There were no complete responses and 18 partial responses, for an overall response rate of 51%. Median time to treatment failure was 6 months (range, 1-18), and the median survival was 9.5 months (range, 1-32). WHO grade 3 toxicity was recorded in up to 8% of patients, flu-like syndrome was a common complaint; one toxic death occurred. CONCLUSIONS: The combination yielded a level of response comparable to that of other cisplatin-based regimens. Larger randomized trials are needed to assess the role of alpha-IFN combined with chemotherapy in advanced NSCLC.

Mitomycin C, 5fluorouracil and folinic acid in combination with alpha 2b interferon for advanced colorectal cancer.

AIMS AND BACKGROUND: This study was conducted to investigate the activity and toxicity of 5fluorouracil folinic acid+mitomycin C combined with alpha 2b interferon in advanced colorectal cancer based upon recent studies suggesting a possible biochemical modulation of 5fluorouracil by interferon. PATIENTS AND METHODS: Between June 1990 and April 1991 25 previously untreated patients with advanced colorectal carcinoma were treated with mitomycin C 10 mg/m2 iv bolus on day 1, 5fluorouracil 375 mg/m2 on days 1 to 4 and folinic acid 200 mg/m2 on days 1 to 4 every 4 weeks, combined with alpha 2b interferon 3 million U day continuously. RESPONSE: Of the 25 patients entered into the study, 20 were evaluable for response as 5 patients withdrew due to toxicity (grade 3-4 thrombocytopenia in 4 cases and fatigue in 1). No complete response was recorded, 6 patients had partial remission (30%; 95% confidence interval, 10% to 50%), 4 experienced no change and 10 showed progressive disease. The toxicity of this regimen was significant, particularly myelosuppression. CONCLUSIONS: This combination showed a significant toxicity and low response rate compared with other 5fluorouracil based regimens in advanced colorectal cancer.

ACTH 1-17 effects in oncology.

Since November 1981, 90 cancer patients treated with cytotoxic chemotherapy (CMF, FAC, FAM) have been studied to evaluate whether the administration of Synchrodyn 1-17, 100 micrograms i.m. a day for 15 consecutive days, could reduce some side effects caused by the cytotoxic drugs. Nausea, vomiting and weakness which are the most frequent side effects generally found to be very upsetting to patients, were less pronounced in the treated patients than in patients treated with a placebo. The performance status was not modified by the treatment. Skin pigmentation was noted in the majority of cases and it appeared to be related to the sustained treatment with high dosages of the peptide. Some side effects were observed in the treated patients such as sodium retention and hypertension, hyperglycemia. Successively we have begun to study the circadian rhythm of the cortisol, which often changes during the advanced stages of the illness and which chemotherapy does not seem to alter.

Effects of Lonidamine on murine and human tumor cells in vitro. A morphological and biochemical study.

Lonidamine induces in murine and human tumor cells severe morphological damage of the mitochondria and other cytoplasmic structures both 'in vitro' and 'in vivo'. Biochemical studies have demonstrated that the drug decreases oxygen consumption and lactate production. The sensitivity of human tumor cells is not related to their histotype. Lonidamine's effects on mitochondria, glycolysis, pentose phosphate pathway, and aromatase activity are discussed.

A long-term clinical experience with Lonidamine.

Lonidamine (LNA) has been investigated both alone and in combination with different chemotherapeutic agents in various types of tumors at an advanced stage. Acute and long-term treatments were studied. LNA has been shown to be devoid of the most typical side effects of currently used chemotherapeutic agents. It has revealed a characteristic profile of side effects, comprising myalgia, photosensitivity and altered hearing. LNA alone, tested in a limited number of patients, produced a partial remission in one ovary adenocarcinoma and a stabilization in two breast carcinomas and one microcytoma. When used in combination with chemotherapeutic agents, it potentiated them, particularly in brain metastases and lung adenocarcinomas.

Morphological damage induced in vivo by Lonidamine on human metastatic cancer cells.

Lonidamine was given to several patients affected with different types of neoplasias growing as metastases both in ascites and pleural effusion, and solid cutaneous metastases. The patients with tumor cells in ascites and pleural effusion were treated with Lonidamine per os or in loco injections. In cutaneous metastases, Lonidamine was administered by different routes: (1) per os; (2) local endoarterial; and (3) in association with hyperthermic perfusion with or without antiblastic drugs.

[Chemotherapy of intestinal carcinomas]. / Chemioterapia dei carcinomi intestinali.

It is not easy to weigh up therapeutic and toxic effects in the medical treatment of intestinal cancer. The number of drugs that have demonstrated certain activity in these forms is extremely limited, only 5 FU being definitely active and even this only in a small percentage of patients. 5 FU produces remission in some 20% of cases. It is highly probable that prophylactic treatment with 5 FU increases patient survival as reported by Regelson and other workers, but the resulting damage (hepatic, bone marrow, immunodepression, etc.) must also be assessed and the risk of a second neoplasia should not be forgotten. The personally used association of 5 FU and cyclophosphamide has proved active at least to the same extent as 5 FU alone, while toxic effects were not particularly important. Brilliant but unfortunately temporary results can be obtained by peritoneal PTC in peritoneal carcinomatosis. Good results with respect to the pain symptom have been obtained by associating 5 FU with radiotherapy in non-operable intestinal tumours.

[Experience with chemotherapy in peritoneal carcinosis]. / Esperienze di chemioterapia nella carcinosi peritoneale.

5-FU i.v. and Ptc i.v. and intraperitoneally were used to treat 8 patients in the Ancona Oncology Centre suffering from metastatic peritoneal carcinosis. Tolerance was generally good and where side-effects were observed they were the same as those habitually encountered in patients treated with 5-FU and Ptc. Ascitic effusion disappeared or reduced by more than 50% in almost all cases. General condition thus improved.

Treatment of neoplasia of the bladder with topical application of a synthetic peptide complex preparation: preliminary results.

Preliminary results are reported on the endo-vesical use of a complex of synthetic peptides ('Peptichemio') in 15 patients suffering from bladder neoplasia who were judged to be beyond surgery or radiotherapy. The agent was introduced into bladder in 20 mg doses diluted in 50 ml of 5% glucose and retained for approximately 30 minutes. Treatment was repeated every 5 to 7 days. The disappearance of the neoplastic mass in 13% of the cases and its reduction in a further 53% encourage the continued use of the preparation in local regional therapy of bladder neoplasia, and the findings help to establish treatment times and doses. For the moment, the authors recommend increasing the interval between treatments to 10 days or more once the neoplastic mass has been reduced or disappeared.

Anxiety therapy in the neoplastic patient.

A clinical study was carried out in 73 neoplastic patients suffering from anxiety and other emotional upsets to assess the effectiveness and tolerance of lorazepam. Patients were given individualised daily doses ranging from 1.5 mg to 3 mg lorazepam for 15 to 60 days. Results, as assessed by the response of anxiety, tension, erethism and insomnia, showed that only 4 (5%) patients failed to obtain some relief. There was complete disappearance of all symptoms in 29 (40%) after 15 days, relief of at least one major symptom and reduction in the others in 27 (37%), and slight reduction in one or more symptoms in 13 (18%) patients. Side-effects were minimal and disappeared within a few days with continued treatment.