Cancer treatment reports最新文献

Echinomycin was administered to patients with advanced carcinoma in escalating doses ranging from 60 to 1500 micrograms/m2 given weekly by 15-minute iv infusions for four doses, with a subsequent 2-week rest period. Dose-limiting nausea, vomiting, and anorexia associated with varying degrees of renal and hepatic dysfunction proved dose-limiting at the 1500-micrograms/m2 level. Thrombocytopenia was noted in 15% of patients receiving greater than or equal to 700 micrograms/m2 and was severe in 11% without an evident dose-response relationship. Leukopenia was rare and mild when encountered. Allergic reactions were observed. Phase II trials are feasible using a dose schedule of 1200 micrograms/m2/week X 4 weeks.

Using a high-performance liquid chromatographic method coupled with fluorimetric detection, we evaluated plasma pharmacokinetics of doxorubicin (DX) and tissue distribution in seven patients suffering from locally advanced breast cancer. Tumor biopsies were performed 30 minutes and 24 hours after DX injection. In addition at 48 hours, during surgery, biopsies were obtained from primary breast cancer, nodes, and other accessible tissues, and DX concentrations were analyzed. A triexponential equation gave the best fit for plasma levels and the values (mean +/- SE) were: elimination half-life, 37.6 +/- 4.9 hours; volume of distribution, 605 +/- 61 L/m2; and clearance 200 +/- 27 ml/min/m2. There was greater interindividual variability in tumor DX concentrations than in plasma concentrations. DX reached much higher (range at 48 hrs, 1.54-14.17 micrograms/g) and longer-lasting concentrations in tumor than in plasma. At 48 hours tumor concentrations were 55.2-337.4 times the plasma concentrations. DX concentrations in normal breast were lower or similar to those in breast carcinoma. DX levels were very low in fat and skin, slightly higher in muscle, and very high in normal or metastasized lymph nodes.

Fourteen patients with malignant carcinoid tumors were treated with rDNA alfa 2b interferon by sc injection three times per week. Treatment was started at a dose of 2 milliunits/m2, with escalations to 3, 5, 7, and 10 milliunits/m2 at 2-week intervals depending on toxicity. No objective tumor regressions were seen, but five of 14 patients (36%) had 50% reduction in 24-hour 5-hydroxyindoleacetic acid excretion and six of nine (67%) with carcinoid syndrome had a good symptomatic response. Biochemical responses occurred during the first 8 weeks of treatment, and escalation of the dose of interferon did not increase the response rate. The rDNA alfa 2b interferon has activity in patients with the carcinoid syndrome and should be used at a low dose (2-3 milliunits/m2) until symptoms recur.

The interaction of methotrexate and/or cyclophosphamide with the pharmacokinetics of 5-fluorouracil (5-FU) was studied in tumor-bearing WAG/Rij rats. Four groups were formed including treatment with single-agent 5-FU (eight rats); 5-FU plus methotrexate (11 rats); 5-FU plus cyclophosphamide (12 rats); and 5-FU, cyclophosphamide, and methotrexate (13 rats). The area-under-the-plasma-concentration/time curve, total-body clearance, elimination half-life, mean residence time, and steady-state volume of distribution were computed and compared. The mean residence time and elimination half-life of 5-FU increased when methotrexate was included in the combination. The increase was significant (P less than 0.05) for 5-FU, cyclophosphamide, and methotrexate versus 5-FU and cyclophosphamide.

Trilostane, an inhibitor of the production of adrenal estrogens, was administered, together with dexamethasone, to 97 eligible postmenopausal women with advanced breast cancer. Seventy-four patients who had either received trilostane for a minimum of 10 weeks or whose disease had progressed while on trilostane before this period were assessed for tumour response. Eighteen patients (25%) had objective responses (two complete, 16 partial); a further 21 patients had stable disease. The response rate among all 97 patients, including those not treated for a minimum 10-week period, was 19%. Thirty-two of 97 patients reported adverse reactions which were attributed to trilostane and/or dexamethasone. Therapy was stopped for 15 patients, and the dose of trilostane was reduced for ten. Diarrhea was the commonest side effect, being reported in 16 patients, of whom nine stopped treatment. Trilostane, given with a corticosteroid, is an effective alternative hormonal agent acting by adrenal blockade for postmenopausal women with advanced breast cancer.

Forty children with multiply relapsed cancers received iv melphalan at three doses: 30 mg/m2, 45 mg/m2, and 60 mg/m2. The hematologic toxicity was severe and protracted at all dose levels, whether or not the bone marrow was involved with tumor. Of 39 evaluable patients, 37 had grade 3 or 4 hematologic toxicity. Nonhematologic toxic effects were infrequent and not severe. Two complete responses (Hodgkin's disease, rhabdomyosarcoma), eight partial responses, and 30 failures were seen. There appeared to be a very narrow margin between efficacy and toxicity. Further study of melphalan in pediatric tumors may be warranted in special circumstances: in higher doses (greater than 100 mg/m2) as cytoreduction therapy for specific cancers with marrow rescue, or as part of combination therapy in certain cancers (eg, lymphoma, sarcoma), possibly at doses of 20 to 30 mg/m2 every 4 weeks.

Forty patients with locally extensive or metastatic squamous cell carcinoma of the esophagus were registered onto a phase II trial employing cisplatin, vinblastine, and mitoguazone. Of 36 eligible patients, four (11%) had partial responses. None had received prior chemotherapy or radiation therapy. Toxicity was mild to moderate and consisted mostly of nausea and vomiting. The activity of this regimen at the doses and schedule used was minimal. More aggressive use of therapy should be considered for further trials.

The continuous infusion of cytarabine, daunorubicin, and etoposide offers several theoretical advantages over bolus infusion in the treatment of acute nonlymphocytic leukemia. To date, this approach has been limited by the need for three separate iv lines. The in vitro stability and compatibility of these three agents were therefore evaluated. Solutions of 200 mg of cytarabine, 25 mg of daunorubicin, and 300 mg of etoposide per 750 ml of 5% dextrose and 0.45% saline were prepared alone and in combination. The solutions were evaluated visually, spectrophotometrically, and by high-pressure liquid chromatography (HPLC) twice daily for 72 hours. Precipitates or color changes were not noted. Changes in the patterns of the spectral scans and chromatographs were not observed. Concentrations of the drugs as assessed by HPLC were stable over the 72-hour period of observation for both individual and combined drug preparations. In conclusion, cytarabine, daunorubicin, and etoposide are stable and compatible in vitro for at least 72 hours. These drugs can therefore be administered together by continuous infusion using a single iv line.