Androgen and estrogen metabolism was investigated in the hormone-dependent human breast cancer cell line MCF-7 and its two hormone-resistant sublines MCF-7/LCC1 and MCF-7/LCC2. Using the product isolation method, the activity of aromatase, 5alpha-reductase, 3alpha/beta-hydroxysteroid oxidoreductase and 17beta-hydroxysteroid oxidoreductase were investigated isolating the following steroids: estriol (E3), estradiol (E2), estrone (E1), 3alpha/beta-androstanediol (A-diol), testosterone (T), dihydrotestosterone (DHT), androsterone (AND), androstenedion (4-AD) and androstanedione (A-dion). For all experiments, cells were preincubated with cortisol and subsequently incubated with [14C]T or [14C]4-AD as the substrate in medium without phenol red and with serum charcoal stripped of steroids. The results showed no aromatase activity in any of the cell lines under the experimental conditions used, and preincubation with cortisol had no effect on the enzyme activity. With [14C]T as the substrate, the metabolized level of DHT was very similar in the three cell lines, though MCF-7/LCC1 and MCF-7/LCC2 utilized the substrate to a much lesser extent. The amount of DHT and 4-AD produced were comparable in the two hormone-resistant cell lines, while the amount of 4-AD was significantly higher in MCF-7 cells. No differences in enzyme activity were found in the three cell lines when [14C]4-AD was used as the substrate. This study showed an altered androgen metabolism in the MCF-7/LCC1 and MCF-7/LCC2 sublines compared to the parent MCF-7. However, since treatment with DHT and T inhibited cell growth equally well in all three tumor cell lines, it is unlikely that the found differences in steroid metabolism was involved in the acquisition of the endocrine resistance of the two MCF-7 sublines.

Aminoglutethimide↗

PubMedDate not supplied

Clinical trial of the oral form of a new podophyllotoxin derivative, VP-16-213 (NSC-141540), in patients with advanced neoplastic disease.

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Administration, Oral↗

PubMedDate not supplied

5-FU in the treatment of small cell anaplastic carcinoma of the lung: a phase II trial.

The effect of 5-FU as a single agent in small cell anaplastic carcinoma of the lung was evaluated in 26 patients. All patients had received prior chemotherapy. Ten patients were treated with 5-FU doses of 600 mg/m2 iv on Days 1--5, followed by 1000 mg/m2 iv on Day 22 and then every second week. Among eight evaluable patients, partial remissions of 42--45 days' duration were seen in three cases. However, toxic reactions, consisting of thrombocytopenia (less than 50,000/mm3) in five cases and leukopenia (less than 1000/mm3) with septicemia in two patients, were unacceptable. Therefore, the remaining 16 patients were treated with 400 mg/m2 iv daily for 5 days, while the maintenance dosage of 5-FU remained unchanged. With this dosage the hematologic toxicity was moderate, but no responses were observed. It is concluded that 5-FU has a low order of activity in previously treated patients with small cell anaplastic carcinoma of the lung.

Aged↗

PubMedDate not supplied

Vindesine in the treatment of small cell anaplastic bronchogenic carcinoma.

The antineoplastic activity of vindesine was evaluated in a phase II trial in patients with small cell anaplastic bronchogenic carcinoma. All patients had been treated previously with vincristine, CCNU, cyclophosphamide, VP-16-213, methotrexate, and doxorubicin. In some of the patients, the primary tumor had also been irradiated, and some patients had received 5-FU or procarbazine. The dose of vindesine was 4 mg/m2/week iv, modified according to hematologic and neurologic side effects. Twenty-six of 32 patients included in the trial were evaluable. Objective response was observed in seven patients (27%). The median duration of response was 35 days (range, 28-90), the response occurring within 14 days after initiation of treatment. Dose modification of vindestine was necessary in 80% of the patients because of hematologic toxicity, while neurotoxicity made dose reductions necessary in about one half of the patients. The study demonstrates that vindesine is active against small cell bronchogenic carcinoma, with apparent lack of clinical cross-resistance to vincristine in previously heavily treated patients.

Antineoplastic Agents↗

PubMedDate not supplied

CCNU, melphalan, methotrexate, and prednisone (CAMP) versus cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in the treatment of advanced breast cancer in postmenopausal women.

Sixty-nine postmenopausal patients with advanced breast cancer were randomized to receive treatment with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or CCNU, melphalan, methotrexate, and prednisone (CAMP). Response rate (partial and complete remission) was significantly higher with CMF (50%) than with CAMP (20%). Hematologic toxic effects were equally pronounced with the two combinations as were the other side effects with the exception of alopecia, which occurred most frequently with CMF.

Aged↗

PubMedDate not supplied

Treatment of small cell lung cancer: the Copenhagen experience.

The present article is a review of recent treatment protocols for patients with small cell lung cancer (SCCL) treated in Copenhagen from 1985 to 1990. Furthermore, preliminary data on long-term survivors (> 5 years) from 9 treatment protocols since 1973 are reviewed. For 484 patients < or = 70 years old, no survival difference was observed between 2 platinum (cis-platinum or carboplatin) containing regimens, while the survival was better in these two induction regimens compared to an alternating control arm. For patients > 70 years old, Etoposide (VP-16) and Teniposide (VM-26) were compared in a randomized fashion. Both drugs were highly active, and no significant difference in activity was observed. All together 1527 patients have been included in clinical trials in the Copenhagen Lung Cancer Study Group since 1973. The rates of 5- and 10-years survivors were 3.5% and 1.8% respectively. Long-term survival can be achieved in all stages of SCCL.

Aged↗