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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.

Adult↗

Enhanced nitrosourea cytotoxicity in cell culture by sodium butyrate.

In HeLa S3 cells, sodium butyrate was found to potentiate the cytotoxicity of chloroethylnitrosoureas and alkylating agents in vitro. Using a soft-agar colony-forming assay, 2.5 and 5.0 mM sodium butyrate pretreatment for 22 h increased the cell killing efficacy of both methyl- and chloroethylnitrosoureas by between 30 and 70%. The potentiation of cytotoxicity of bifunctional nitrogen mustards by butyrate was less than that of nitrosoureas, with a 15-30% increased cell kill at 5 mM butyrate. Sodium butyrate per se reduced plating efficiency and caused growth delay if residual levels (calculated at 100 microM for starting concentrations of 5 mM) were not removed by washing prior to plating.

Butyrates↗

Three alkaloids as selective destroyers of cancer cells in mice. Synergy with classic anticancer drugs.

Alstonine, serpentine and sempervirine, when used at appropriate concentrations cure a relatively important proportion of BALB/C mice inoculated with transplantable YC8 lymphoma ascites cells, as well as Swiss mice bearing Ehrlich ascites carcinoma cells. The development of some solid tumors was only partially prevented. However, when one alkaloid was administered in association with either 5-FU, daunorubicin, 1-(2-chloroethyl) nitrosourea (CCNU) or cyclophosphamide (CP) to mice bearing either ascites carcinoma cells or solid tumors, a high rate of cure was obtained without toxicity. The role of the three alkaloids in the curing of mice and prevention of carcinogenesis is discussed.

Alkaloids↗

Energy status in HeLa cells after treatment with an arresting anticancer drug.

The energy status of HeLa cells arrested in the G2 phase of the cell cycle by the antineoplastic agent cis-acid was compared with that of normal G2-phase-synchronized cells. The results showed that treatment with the drug has significantly decreased the adenylate pool, adenylate energy charge and phosphorylation potential.

Adenine Nucleotides↗

Combination chemotherapy with methotrexate, adriamycin, cyclophosphamide and CCNU (MACC) for nonsmall cell lung cancer. 4-year experience with 92 patients.

Ninety-two nonsmall cell lung cancer (NSCLC) patients were treated with a combination chemotherapy containing methotrexate, adriamycin, cyclophosphamide and CCNU (MACC). The regimen was administered in the dose and schedule originally reported. Median survival for all patients was 32 weeks. Only 6 patients demonstrated an objective response with a median survival rate of 51 weeks. The remaining 70 evaluable patients were nonresponders. These latter patients had a survival probability reduced to 29 weeks. Median time to progression for the whole group was 17 weeks. Partial responses were seen in 3 squamous, 1 large cell carcinoma and 1 adenocarcinoma. One patient with bronchiolo-alveolar carcinoma had complete disease regression and is still alive 136 weeks after starting treatment. Toxicity was significant with 2 treatment-related deaths. The major toxic effects consisted of myelosuppression, nausea, vomiting, and stomatitis. Alopecia was nearly universal; a mild cardiac, renal, or hepatic toxicity was relatively infrequent. Polychemotherapy with MACC regimen may benefit a few selected patients with NSCLC, but its overall antitumor efficacy appears to be very limited.

Adult↗

Treatment of resistant Hodgkin's disease with CCNU, etoposide and prednimustine (CEP).

Starting in January 1984, 63 patients with resistant Hodgkin's disease received CEP as salvage-usually third-line-chemotherapy. Complete response (CR) was achieved in 3%, partial response (PR) in 51%. The median duration of remission (CR + PR) was greater than 15 months. Treatment was generally well tolerated. Our results confirm that CEP is an effective therapeutic regimen in resistant Hodgkin's disease.

Adolescent↗

Optimal control of cyclophosphamide-induced emesis.

Cyclophosphamide induces moderate to severe emesis. The severity of emesis is dependent on the dose of cyclophosphamide and on the addition of other cytotoxic drugs. A review of the literature dividing studies according to the dose of cyclophosphamide and the specific cytotoxic combination shows that ondansetron plus dexamethasone provides optimal antiemetic therapy in patients receiving standard or high-dose cyclophosphamide (> or = 450 mg/m2). These studies also show that it is important to give antiemetic therapy to cover the prolonged duration emesis and nausea induced by these regimens, e.g. intravenous CMF/(F)AC/(F)EC. For continuous 'oral' (low-dose) CMF chemotherapy, oral ondansetron or oral metoclopramide plus intravenous (or possibly oral) dexamethasone are effective antiemetic therapies.

Antiemetics↗

Psoriasis: a review. II.

Notwithstanding the intense interest in systemic cytotoxic therapy in recent years, the great majority in psoriatics are likely to go on needing topical therapy with tar, dithranol or corticosteroids, and a welcome trend is the spreading of interest in day care centres such as those in Paris (GRUPPER), Stockholm (THYRESSON), Stanford (FARBER) and San Francisco (CRAM) evolving from the out-patient regimes advocated by INGRAM in Leeds a generation ago.

Adrenal Cortex Hormones↗

Preradiation chemotherapy with VM-26 and CCNU in patients with glioblastoma multiforme.

AIMS AND BACKGROUND: The objective of the study was to evaluate the efficacy of combined chemoradiation in patients with newly diagnosed glioblastoma multiforme. The main end points were time to progression and overall survival. METHODS: Thirty-one patients with glioblastoma multiforme underwent surgery whenever possible and then received intravenous VM26 (120 mg/m2) and oral CCNU (120 mg/m2) for three cycles followed by radiotherapy (60 Gy). RESULTS: Surgery consisted of a complete resection in 39% of patients, partial resection in 35% and a biopsy in 26%. Sixteen patients had clinical or radiological evidence of progression during or after chemotherapy. Hematologic toxicity was mild. Forty-five percent of patients received the scheduled dose of radiation. The outcome was disappointing, with a median time to progression of 18 weeks and median survival of 37.17 weeks. CONCLUSIONS: The survival of patients with glioblastoma multiforme remains disappointing. Multimodal therapy does not seem to modify the evolution of the tumor. Stratification according to prognostic factors might detect a potential benefit of other therapeutic approaches.

Administration, Oral↗

Ten years experience with Ewing's sarcoma.

The series comprises 57 consecutive patients with Ewing's sarcoma admitted to the National Cancer Institute of Milan from 1965 to 1976. In 75% the diseas was confined to one bone, while in 25% multiple bone and/or visceral lesions were present. Patients with clinically localized tumor treated before 1971 with local therapy, showed a median disease-free survival of 5 months. After 1971, radiotherapy and/or surgery to local tumor was combined with multiple drug chemotherapy (ADM, VCR, CTX) and the projected median disease-free survival increased to 24+ months. In previously untreated patients with advanced tumor adriamycin, used as single drug, achieved an overall response rate of 73%. This is comparable to that achieved by a new combination including ADM, VCR, CTX, CCNU (75%). This multiple drug regimen is, however, expected to prolong the duration of response.

Adolescent↗

Medical treatment of metastatic renal cell carcinoma.

Thirty five patients with metastatic RCC were observed over a 57 months period in our Division of Radiotherapy and Medical Oncology, and 30 are evaluable for this analysis. MPA was selected as primary treatment agent in 23 patients, VLB singly, in combination with MPA or in combination with CCNU was used in 1.4 and 2 patients. With MPA the TR rate was 3/23 (1 CR and 2 PR). Duration of response for the patient with CR was 6 months whereas for the patients with PR was 21 and 14 months respectively. 4 additional patients showed NC. With VLB-MPA the TR rate was 1/+ (1 PR). Duration of PR was 3 months. The median duration of survival for the 11 patients with CR, PR and NC was 14 months whereas for the 19 patients with NR was 7 months (p < 0.01). TES and TAM showed no or minimal activity as second treatment agents.

Adult↗

Cardiotoxicity of 5-fluorouracil.

A case is reported of cardiotoxicity during a multiple drug treatment with fluorouracil, vincristine and CCNU in a patient with a large bowel cancer without any precedent history of heart disease. The patient had chest pain, with an altered ECG and increased serum levels of alpha HBDH.

Angina Pectoris↗

Combination chemotherapy for metastatic brain tumors.

Forty-four patients with central nervous system metastases were treated with combination chemotherapy (adriamycin, VM 26 and CCNU). The best results were obtained in breast adenocarcinoma and small cell lung carcinoma with multiple, small cerebral metastases and without concomitant visceral involvement at other sites. The potential effectiveness of this regimen to prevent cerebral metastases is discussed.

Adenocarcinoma↗