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Biomedical subjects

W S Fletcher

Publications and source records attributed to W S Fletcher.

At least 127 records · Page 7Linked to original sources
PubMed1976

Studies on adriamycin using a weekly regimen demonstrating its clinical effectiveness and lack of cardiac toxicity.

Adriamycin has been given to 442 patients using the weekly regimen as initially described by Bonadonna et al. Hematologic toxicity and clinical effectiveness have been similar to those described with regimens in which the drug is given every 3 weeks. Stomatitis is more frequent with the weekly regimen than with the usual triweekly regimen. The incidence of electrocardiographic changes and arrhythmias was similar to that reported in other studies. Nine patients received between 500 and 550 mg/m2, nine between 550 and 600 mg/m2, 28 between 600 and 1000 mg/m2, and 22 between 1000 and 2500 mg/m2. None of the patients developed definite evidence of cardiomyopathy although six showed some disturbance of myocardial function. In each of the six patients, factors other than adriamycin cardiotoxicity were believed to play a major role in the myocardial abnormality. The difference between the incidence of cardiomyopathy seen in this series and that previously reported is statistically significant. The reasons for the difference are not clear but are probably related to the schedule that was used.

Adult↗
PubMed1976

Multimodal surgical adjuvant therapy for a broad spectrum of tumors in humans.?

Co-operative investigation of clinical therapy for cancer is used to test hypotheses developed in single institutions and in animal research laboratories. The present studies in a large co-operative organization, the Central Oncology Group, are being conducted in seven major solid tumors in adults; in these studies patients with a poor surgical prognosis are being treated with preoperative or postoperative chemotherapy, preoperative radiotion therapy of these modalities. Results of studies currently underway or recently completed in 1,278 patients are summarized. In most instances, the research has demonstrated little or no apparent improvement in the disease free interval or the survival time from adjuvant therapy, although only on of the studies has been completed and fully evaluated thus far. In carcinoma of the colon and rectum and melanoma, mild toxicity from drug therapy has been associated with statistically significant improvement in survival times. These studies have produced base line information on disease free intervals, time to progression and survival time in patients with cancer who are seen in the participating institutions. These observations are expected to useful in the planning of future adjuvant studies.

Adult↗
PubMed1976

DTIC (nsc-45388) and combination therapy for melanoma. I. Studies with DTIC, BCNU (NSC-409962), CCNU (NSC-79037), vincristine (NSC-67574), and hydroxyurea (NSC-32065).

A total of 270 patients with metastatic malignant melanoma were entered into a randomized chemotherapy study conducted by the Central Oncology Group (COG) over a period of 2 years (COG protocol No. 7130). The study utilized DTIC, CCNU, BCNU, vincristine, and hydroxyurea. The results of therapy with DTIC alone were compared with three combinations: (a) DTIC, CCNU, and vincristine; (b) DTIC, BCNU, and vincristine: and (c) DTIC, BCNU, and hydroxyurea. There were 243 evaluable patients out of 270. The response rate was 17.3% (42 of 243 patients) for evaluable patients and 15.5% (42 of 270 patients) for all patients entered in the study. The results showed no statistically significant difference in the response rates among the four treatment arms. However, several significant points were observed: (a) A 13% response rate was obtained using a combination of agents that included DTIC in patients who had previously shown no response to DTIC used as a single agent. (b) There was a significant difference in survival time when comparing responders to those with no change and to those with progression. (c) Toxicity was noted to be greater in responders than in nonresponders. (d) Two of the four treatment arms were considered most advantageous due to the ease of administration. These treatment arms were DTIC, BCNU, and vincristine and DTIC, CCNU, and vincristine administered in 5-day courses every 6 weeks. (e) The percentage of response and length of survival were significantly greater in patients without brain or liver metastasis. (f) In comparing men to women there was no statistically significant difference in response in rates or durations of response. (g) There was no statistically significant difference in survival when comparing site of primary lesion.

Adolescent↗
PubMed1975

Streptozotocin therapy in 22 cancer patients.

Twenty-two cancer patients were treated with streptozotocin (SZN) in six weekly intravenous doses of 1.0-1.5 g/m2. The results of the initial courses of therapy include 3 complete and 2 partial responses, 11 patients with no change, 4 with progression, and 2 deaths due to tumor progression. Three additional deaths also due to tumor progression occurred in previously responding patients. All responses were in patients with pancreatic tumor. Toxicity consisted of transient proteinuria in 11/15 patients, transient azotemia in 11/18 patients, marked reduction of creatinine clearance in 1 patient, burning pain at site of injection, nausea, and vomiting in 20/22 patients, change of FBS from pretherapy to post-therapy of at least 10 mg/100 ml in 11/17 patients, significantly decreased platelet count in 1/22 patients, decreased Hgb in 2/22 patients, and duodenal ulcer in 2/22 patients. A reduced dosage schedule and combination with other drugs known to be effective in pancreatic tumors deserves further investigations.

Aged↗
PubMed1975

Yoshi 864 (NSC 102627) 1-propanol, 3, 3'-iminodi-dimethanesulfonate (ester) hydrochloride: a phase 1 study.

Yoshi 864 was given i.v. push daily times 5 with 6 weeks' followup. Dose escalation was from 0.25 mg/kg to 2.7 mg/kg. Toxicity and effectiveness were first seen at 1.5 mg/kg. Twenty-five courses were given to 16 patients at or above this level. In 16 of 22 courses, exclusive of CML, thrombopenia and/or leukopenia occurred. Mean platelet and WBC nadirs occurred on day 24 and 29 with recovery taking 1-2 weeks and 2-3 weeks respectively. Hb fell in 11 courses. At 2.7 mg/kg, nausea and vomiting lasting 6-12 days occurred in 3 of 7 courses; during 5 coures patients slept 20 hours a day, and 1 was comatose for 2 days. Two patients with squamous cell carcinoma and 1 with an unknown primary responded. Both patients with CML had clinical remissions. It is recommended that a cooperative Phase II Study in a broad spectrum of human solid tumors including lymphomas and chronic myelocytic leukemia be undertaken at a dose level of 2 mg/kg.

Alkylating Agents↗
PubMed1975

A clinical trial of CCNU (1-(2 chloroethyl)-3-cyclohexyl-1-nitrosourea) (NSC 79037) in advanced ovarian carcinoma.

CCNU is a useful drug in treating advanced ovarian carcinoma. Of patients with advanced ovarian carcinoma 37% responded favorably to CCNU. Thrombocytopenia was the primary toxic reaction. Clinical trials are in progress to compare the relative effectiveness, the degree of cross-resistance, and the difference in toxicity between CCNU and alkylating agents.

Alkylating Agents↗
PubMed1975

Multimodality therapy in the treatment of regionally inoperable melanomas and sarcomas.

Nine patients with regionally inoperable malignant melanoma or soft tissue sarcoma were treated with combinations of intra-arterial chemotherapy, immunotherapy and operation or irradiation or both. Three of the heretofore untreatable patients with melanoma remain clinically free of detectable metastases at three years, three and one-half years and one and one-half years from their recurrence. One nodular melanoma remains well controlled two years after diagnosis, while an additional patient is free of disease several months after therapy. Two of the patients with melanoma died within a year of the onset of the recurrence but maintained the affected limb in useful condition until the time of their death. Two of the three patients with sarcoma remain free of disease at ten and four years. One patient who was known to have distant metastatic disease at the onset of the treatment currently is hospitalized for further therapy for tumor in the para-aortic lymph nodes.

Adult↗