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Biomedical subjects

W S Fletcher

Publications and source records attributed to W S Fletcher.

At least 19 recordsLinked to original sources
PubMed1992

Synergistic cytotoxicity of combinations of dimethyl sulfoxide and antineoplastic agents against P388 leukemia in CD-F1 mice.

We have reported that dimethyl sulfoxide (DMSO) and antineoplastic agents exhibit synergistic cytotoxicity against human tumors in vitro. This study was undertaken to investigate this effect in vivo. Groups of mice were given intraperitoneal (i.p.) injections of P388 leukemia cells. Groups were treated with i.p. injections of either saline, DMSO alone, mitoxantrone hydrochloride (DHAD) alone, methotrexate alone, DHAD in DMSO or methotrexate in DMSO. Combinations of DMSO and DHAD produced 46-61% increases above expected survival, demonstrating synergistic cytotoxicity in vivo. Following confirmatory animal studies, trials utilizing i.p. delivery of antineoplastics in DMSO as treatment for peritoneal tumors should be undertaken.

Animals↗
PubMed1979

Combination chemotherapy for soft-tissue sarcomas: a phase III study.

A total of 144 patients with advanced sarcomas were entered into a randomized prospective protocol with four treatment arms utilizing different combinations of chemotherapeutic agents. Of these, 120 patients (83%) were judged acceptable. Treatment 1: actinomycin-D (Act-D), 0.01 mg/kg IV, days 1--5; phenylalanine mustard (L-PAM), 4 mg PO, days 1--10 every six weeks. Treatment 2: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, days 1--10; vincristine, 1 mg IV, days 1, 8, 15, 22, 29, 36, repeat every six weeks. Treatment 3: Act-D, 0.01 mg/kg IV, days 1--5; L-PAM, 4 mg PO, DAYS 1--10; NSC-1026, 200 mg/kg IV, days 1--6. Treatment 4: Adriamycin, 0.4 mg/kg IV, days 1, 2, 3, 8, 9, 10, then 2XWK starting day 15 (max. 1,200 mg). There was a provision that upon progression of the disease in the first three treatment regimens, patients would be crossed over to Treatment 4. Responses were as follows: 1 - Partial Response (PR) 1/25; No Change (NC) 9/25 (36%). gF2 - NC 17/26 (65%). 3 - NC 13/25 (52%). 4 - Complete Response (CR) 1/41; PR 6/41; (15%); NC 27/41 (66%). Clearly Treatment 4 was the best arm, with a 17% response rate and an initial progression rate of 17%. The only other response was a partial in 1. The difference is statistically significant (H = 17.247, P = 0.0006). If the responders to Adriamycin were analyzed without crossovers, the response rate would be 22% (6/27). (H = 14.079, P = 0.003). Median times to progression were 12.5, 8.7 weeks for 1 and 2, and 5 weeks for 3 and 4. There was no significant difference in the median survival times among the four treatment arms. It appears that Adriamycin as a single drug is superior to the drug combinations and would probably be even more effective used in combination with known active agents.

Antineoplastic Agents↗
PubMed1979

5-FU versus combination therapy with tubercidin, streptozotocin, and 5-FU in the treatment of pancreatic carcinomas: COG protocol 7230.

From May 1972 until May 1976, 105 patients were entered on Central Oncology Group protocol 7230 to compare the combination of streptozotocin, tubercidin, and 5-fluorouracil (5-FU) versus 5-FU alone in the treatment of adenocarcinoma and islet cell carcinoma of the pancreas. Twenty-nine were not evaluable. Thirty-six evaluable cases received 5-FU, and 40 received the combination, with no significant difference in time to progression or survival. Toxicity in the two regimens was somewhat different but was essentially similar in magnitude. Results indicate no benefit in the treatment of adenocarcinoma of the pancreas with the three-drug combination over 5-FU alone. All of the islet cell tumor patients benefited from the combination by response or arrest of progression of disease. Further study should be directed toward the use of this combination in the treatment of functioning and non-functioning islet cell tumors of the pancreas.

Adenocarcinoma↗
PubMed1979

Human umbilical cord vein allograft arteriovenous fistula for chemotherapy access.

Seven patients who received chronic chemotherapy and required vascular access underwent construction of an arteriovenous fistula of the leg using gluteraldehyde-tanned human umbilical cord vein allografts. No wound or graft complications have occurred and patient tolerance of the operative procedure and subsequent use of the fisulas for chemotherapy has been excellent. Our preliminary results suggest that the use of umbilical vein allograft arteriovenous fistulas is quite satisfactory for long-term chemotherapy access.

Adult↗
PubMed1978

The use of antiestrogens tamoxifen and nafoxidine in the treatment of human breast cancer in correlation with estrogen receptor values. A phase II study.

Twenty-five patients with measurable metastatic breast cancer and assays for estrogen receptor (ER) were studied. Of the 16 ER positive patients on anti-estrogen therapy, one had complete disappearance of all tumor for seven months and seven patients had more than 50% reduction in their measurable tumor for an average duration of 8.8 months. Seven other ER positive patients had stabilization of their tumors for an average interval of 8.4 months. Only one of the 16 ER positive patients progressed promptly. Conversely there was only one partial response in the nine ER negative patients and only two ER negative patients had stabilization of disease. Six out of nine ER negative patients progressed promptly. Correlation existed between the duration of response and absolute estrogen receptor level of the tumor. There may be a positive correlation between the response to antiestrogen therapy and response to endocrine ablation but prospective studies must be done to further define the role of antiestrogens in this regard.

Breast Neoplasms↗
PubMed1978

Anterior resection and primary anastomosis following high dose preoperative irradiation for adenocarcinoma of the recto-sigmoid.

Preoperative irradiation for adenocarcinoma of the rectum and sigmoid does not always limit the surgery to an abdominoperineal resection. From 1960 to 1976 anterior resection and primary anastomosis of the bowel has been performed in 13 patients with adenocarcinoma of the rectum and sigmoid whose tumor had been irradiated with 5000 rads with small pelvic fields. The inferior surgical resection line was within or very near the edge of the radiation field in 10 patients. In no instance was the superior resection line irradiated. Compared to a group of 79 patients treated with anterior resection only, the preoperatively irradiated patients had lower incidence of pelvic and anastomotic tumor recurrence, but a higher incidence of anastomotic leak and subsequent adhesions and intestinal obstruction. We stress that if irradiated rectum is considered for forming the anastomosis, a temporary "protective colostomy" should be strongly considered at the time of the surgery.

Adenocarcinoma↗
PubMed1978

Adriamycin, bleomycin, and CCNU as effective induction chemotherapeutic agents in advanced squamous cell carcinoma (COG Protocol 7333).

Twenty-six member institutions of the Central Oncology Group entered 154 patients in this two-armed, phase III study comparing the effects of adriamycin, bleomycin, and CCNU against a variety of squamous cell carcinomas. The combination of adriamycin and bleomycin produced a 43% overall response rate in primary tumors of the head and neck, which included two complete responses. This compares favorably to the results obtained with methotrexate and other agents previously reported. The combination of adriamycin and bleomycin will probably be the most useful for induction chemotherapy because both drugs have cumulative toxicities and the duration of response to this combination is short.

Aged↗
PubMed1978

Yoshi 864 (1-propanol, 3,3'-iminodi-, dimethanesulfonate [ester], hydrochloride): a phase II study in solid tumors.

Two hundred and eight acceptable patients were treated with Yoshi 864 (2 mg/kg/day by iv push X 5 days repeated once every 6 weeks). Toxicity was minimal. There was an overall response rate of 11%. Cross resistance with other alkylating agents may not be present. Because of its lack of toxicity, Yoshi 864 should be further evaluated in chronic myelocytic leukemia, lymphomas, and carcinomas of the ovary and bladder where significant responses were seen. It should also be evaluated in combinations as a replacement for other alkylating agents which cause more nausea and vomiting.

Alkylating Agents↗
PubMed1977

Regional intra-arterial infusion of adriamycin in the treatment of cancer.

Forty patients with otherwise untreatable advanced carcinomas received arterial infusions of adriamycin. Significant responses were seen in five of nine tumors of the bladder, two of five hypernephromas, two of two islet cell tumors, three of five sarcomas and one of two metastatic tumors of the breast. One patient with advanced transitional cell carcinoma of the bladder had no tumor at the time of a subsequent resection. There were no responses seen in two oat cell tumors metastatic to the liver, one seminoma of the retroperitoneal space metastatic to the liver, one squamous cell tumor metastatic to the liver, one squamous cell of the vulva, one carcinoma of the cervix uteri and one cloacogenic carcinoma. these responses in advanced tumors are exciting. The use of this technique to reduce tumor bulk prior to operation, irradiation, adjuvant chemotherapy and immunotherapy may allow a significant breakthrough for such tumors as sarcomas, hypernephromas and transitional cell carcinomas of the bladder. Further studies will be pursued using this concept.

Adenocarcinoma↗
PubMed1977

A ten-year study of carcinoma of the pancreas.

During the 10 years from 1965 through 1974, 86 patients with adenocarcinoma of the pancreas were diagnosed or referred for treatment at the University of Oregon Health Sciences Center. The average age and survival in these patients is not significantly different from other published series. Only four patients had resectable tumors, and of these two survived over twelve months. Eight other patients also survived over twelve months, and no two of these had the same treatment regimens (although nine of the ten long-term survivors received some form of chemotherapy). Fourteen patients received a combination of chemotherapy and radiation therapy. While their average survival was only two months longer than that of the entire series, three were long-term survivors. Over 75% had significant palliation; this suggests that this treatment should be considered in selected cases.

Adenocarcinoma↗
PubMed1976

Preoperative radiotherapy for adenocarcinoma of the rectosigmoid.

Ninety-seven patients with adenocarcinoma of the rectosigmoid have been treated with high dose (5000-6000 rad) preoperative irradiation from 1960 through 1972 at the University of Oregon Health Sciences Center. Fifty-seven were initially clinically resectable and 40 were initially inoperable. Forty of the 57 initially clinically resectable patients had "curative" resections and are at risk for more than 5 years. An increase in 5-year survival (from 38% to 53%) and an absence of pelvic recurrence have occurred in those patients receiving preoperative irradiation and "curative" resection. Four of the 40 initially inoperable patients are alive without tumor. Three of the four survivors had irradiation and surgery; one had irradiation only. An additional four patients had no evidence of tumor at death. Tumor was totally sterilized by irradiation and nine patients and reduced to microfocal extent in an additional three of the 97 patients. Incidence of complications was no greater than has been reported in a surgical series from the same institution.

Adenocarcinoma↗
PubMed1976

Treatment of advanced malignancy with CCNU (NSC 79037): a phase II cooperative study with long-term follow up.

CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea, NSC-79037) was used to treat advanced malignancies in 329 evaluable patients. The treatment dosage was 130 mg/m2 for patients with adequate bone marrow reserve and 100 mg/m2 for those with compromised bone marrow. Oral treatment was repeated at 6-week intervals unless hematologic toxicity intervened. There were four complete responses: two in ovarian cancer, one with small cell carcinoma of the lung, and one with melanoma. Tumor response greater than 50% reduction in tumor size occurred in 39 patients (11.9%) while stable disease (no change or decrease or increase of less than 50% in tumor size) was noted in 152 patients (46.2%). Tumor progression occurred in 130 cases. Melanomas and ovarian and lung cancers had the highest response rates. Bone marrow depression was the major side effect of treatment; there was a significant positive correlation between the severity of leukopenia and thrombocytopenia and tumor response to treatment.

Humans↗
PubMed1976

A randomized pilot study comparing two regimens in the treatment of squamous cell carcinoma.

Thirty-five patients with epithelial carcinomas not considered to be surgically resectable were randomized to receive two different chemotherapy regimens. Regimen 1 was CCNU followed by bleomycin, and Regimen 2 was a combination of CCNU, bleomycin, methotrexate, and vinblastine. Five of 14 patients treated with CCNU-bleomycin had partial responses. Three of 15 patients treated with the four-drug combination had a partial response. The toxicity of the four-drug regimen was significantly greater than that of the two-drug regimen, while the response rate was greater among those patients treated with two drugs. No significant clinical infections occurred despite the fact that leukopenia and thrombocytopenia were more severe and frequent with the four-drug regimen. Most importantly, the two-drug regimen is well tolerated as an outpatient procedure. Two of the two-drug and one of the four-drug recipients were converted from an inoperable to an operable state. In view of the fact that there has not heretofore been an effective chemotherapeutic regimen for Stage III and IV squamous carcinoma, this is a significant observation. It is of note that patients with squamous cell carcinoma of the head and neck were those who responded best to this treatment, although the treatment is worthy of consideration for advanced squamous carcinoma in other areas.

Bleomycin↗