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Biomedical subjects

W S Fletcher

Publications and source records attributed to W S Fletcher.

At least 91 records · Page 5Linked to original sources
PubMed1982

The importance of treatment sequence in advanced and metastatic carcinoma of the breast.

From 1965 to the present, 287 patients with advanced and metastatic carcinoma of the breast have been treated according to a uniform philosophy of sequential therapy. Surgical castration was the initial procedure for premenopausal women and for postmenopausal women with clinical or laboratory evidence of endocrine responsive tumors. Tumor progression following castration was treated with major endocrine ablation, either adrenalectomy or hypophysectomy. Patients who relapsed following major ablation were treated with antiestrogen therapy as it became available. Nonresponders to major ablation and patients relapsing after antiestrogen therapy were treated with combination chemotherapy including cytoxan, methotrexate, 5-fluorouracil, and vincristine followed by adriamycin alone or in combination. Progression following chemotherapy was treated with additive hormonal therapy. Radiation therapy was used throughout for the control of localized disease, usually following complete hormonal ablation, except in cases of brain and spinal metastatic disease. The median survival for the entire group was 40.5 months from the onset of metastatic disease. Patients who responded to both oophorectomy and major ablation had a median survival of 61 months, which compares favorably to survival of 14 to 22 months reported in major combination chemotherapy trials. Survival following this method of sequential therapy is superior to other plans of management.

Adrenalectomy↗
PubMed1982

Multiple simultaneous and sequential estrogen receptor values in patients with breast cancer.

Fifty-nine women had multiple estrogen receptor assays done, either simultaneously or sequentially. Eighty-six percent of the patients who had multiple synchronous estrogen receptor assays from various metastatic sites showed no significant discrepancy in estrogen receptor values. When estrogen receptor assays were done sequentially without intervening therapy, 83.5 percent of the patients maintained their initial positivity or negativity. However, when the second estrogen receptor determination was preceded by either chemotherapy or hormonal therapy, 33 percent of the patients had a significant discrepancy in estrogen receptor values. The most common discrepancy was estrogen receptor-positive tumors becoming estrogen receptor-negative, although a small number of patients were found whose receptor values became more positive after hormonal ablation.

Antineoplastic Agents↗
PubMed1982

Liposarcoma of the leg.

Forty-eight patients with liposarcomas of the leg were reviewed. Patients were treated by three approaches: wide local excision, amputation, and regional hyperthermic perfusion. Deaths from distant metastases occurred at a similar rate in all groups. The local recurrence rate was 43 percent in the wide excision group and 29 percent in the amputation group. No perfused patient had a local recurrence. This study demonstrates that hyperthermic regional perfusion and excision are superior to wide excision or amputation in preventing local recurrence for a liposarcoma of the leg and allow salvage of a functional limb.

Adult↗
PubMed1982

The treatment of state I melanoma of the extremities with regional hyperthermic isolation perfusion.

One hundred twenty-two clinically Stage I malignant melanoma patients were treated prospectively in a nonrandomized trial by hyperthermic isolation perfusion with l-phenylalanine mustard (l-Pam), regional lymphadenectomy (RL), and wide local excision (WLE) between April 1965 and July 1980. There were 31 males and 91 females. All primary lesions were retrospectively microstaged by Clark's levels and Breslow's thickness criteria by one of the senior authors. Morphologically, 71% were superficial spreading melanomas (SSM), 16.5% were nodular melanomas (NM), and 11.9% were acral lentiginous melanomas. Survival by microstaging and morphology are reported in Table 1. Eighty-one per cent of all patients were disease-free at five years. Twenty-three patients (18.8%) recurred and of these, 15 died of their disease. This included six of the seven patients with histologically positive lymph nodes. Complications were not only acceptable but preventable and will be discussed. Microstaging provides a valid basis by which to compare treatment regimens and, more importantly, a valid criteria by which to select treatment for a given patient. These data compare favorably with other reported series. At the time these studies were initiated, five-year survivals for clinically Stage I and II melanoma were roughly 55% and 15%, respectively. Existing data clearly indicate that hyperthermic isolation perfusion with RL is superior to WLE and warrants further study in selected patients.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed1982

Endocrine ablation and hepatic artery infusion in the treatment of metastases to the liver from carcinoma of the breast.

Seventy-one women with disseminated carcinoma of the breast metastatic to the liver were treated using one of three treatment regimens. All the patients received intravenously administered cytotoxic chemotherapy. Thirty-five women were treated with hepatic intra-arterial infusion of chemotherapy in combination with hormonal ablative procedures. Twenty-three patients were treated by hormonal ablation procedures without intra-arterial infusion. A third group of 11 women underwent hepatic artery infusion without hormonal ablative procedures. The women treated with both intra-arterial infusion and hormonal ablation had a mean survival time of 21 months from the documentation of hepatic metastases. The second group, those who underwent ablation but not infusion, had a mean survival time of 15 months from the documentation of hepatic involvement. Both of these figures compare favorably with the expected survival time of three to nine months. We believe that these results demonstrate the need for aggressive multimodality therapy in women with hepatic metastasis and further demonstrate the positive role of endocrine manipulation in metastatic carcinoma of the breast, even in patients with predominantly visceral disease.

Adrenalectomy↗
PubMed1982

Tamoxifen and oophorectomy in the treatment of recurrent breast cancer: a Southwest Oncology Group Study.

The relatively short survival following chemotherapy in patients with metastatic carcinoma of the breast and the introduction of antiestrogens has led to renewed interest in the hormonal therapy of breast cancer. Pritchard et al. (Cancer Treat. Rep., 64: 787-796, 1980) have recently stated that response to the antiestrogen tamoxifen (TAM) strongly predicts a subsequent response to oophorectomy in premenopausal patients. The Southwest Oncology Group administered TAM to pre- and postmenopausal women with first recurrence of breast cancer. Following response and subsequent relapse, or after no response, patients underwent an oophorectomy while continuing on TAM. None of 14 premenopausal patients who responded to TAM had a response to oophorectomy plus TAM, while 5 of 22 had a remission with oophorectomy plus TAM after initially failing with TAM alone. The reverse was seen in postmenopausal women; 4 of 18 responders to TAM subsequently responded to oophorectomy plus TAM, but none of 18 TAM failures responded to oophorectomy plus TAM. These results suggest that in the premenopausal women the TAM dose may be insufficient to block all estrogen action and that oophorectomy, by removing the major source of estrogen, can result in a more effective antiestrogen action of TAM leading to a response. No explanation is readily available for the results in postmenopausal patients.

Breast Neoplasms↗
PubMed1981

DTIC and combination therapy for melanoma: III. DTIC (NSC 45388) Surgical Adjuvant Study COG PROTOCOL 7040.

A prospectively randomized study of postoperative chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC) was conducted by the Central Oncology Group from 1972 until 1976. Of 174 patients operated upon for melanoma and entered into the study, 87 were randomly selected to receive DTIC, four courses in 12 months, at 4.5 mg/kg/d x 10. One-hundred-sixty-five (95%) of the cases were evaluable, including 40 high risk Stage I, 96 Stage II, and 29 Stage III cases. At a median follow-up period of 2.5 years, the control group had a better median disease-free interval (40 weeks vs. 73 weeks), median survival time (103 weeks vs. 133 weeks), and percentage of patients living free of disease (28% vs. 44%) than the DTIC-treated group. While disease-free interval appeared to be improved in the 25% of patients on DTIC therapy who developed thrombocytopenia, the overall effect of postoperative DTIC therapy was apparently not beneficial (P less than 0.05).

Adolescent↗
PubMed1981

Dimethyltriazenoimidazole carboxamide therapy of islet cell carcinoma of the pancreas.

Four patients with metastatic glucagonoma and one patient with metastatic diarrheogenic islet cell carcinoma of the pancreas were treated with dimethyltriazenoimidazole carboxamide (DTIC), 250 mg/M2 daily for five days repeated every four weeks. All patients responded clinically and chemically in one or more ways by a reduction in plasma glucagon levels, improved glucose tolerance, decreased measureable tumor, weight gain, and resolution of necrolytic migratory erythema and diarrhea. This experience and other cases from the literature call for the investigation of DTIC as the initial therapy in metastatic islet cell carcinoma of the pancreas and as being of possible benefit in other tumors of neuroendocrine origin.

Adenoma, Islet Cell↗
PubMed1981

Hormone receptors in male breast carcinoma.

It is well established that approximately 60% of female breast cancers contain estrogen receptors (ER+). The hormonal receptor status of male breast cancers remains relatively unknown. Tumor tissue from 14 patients has been reviewed at the University of Oregon Health Sciences Center. Specimens of all 14 patients were ER+ with a range of 5.5 to 374 fmol/mg protein. Eight of 12 patients had tumors which also contained progesterone receptors (PR+) with a range of 42 to 1852 fmol/mg protein. Nine patients were treated by modified radical mastectomy, two by radical mastectomy, one by simple mastectomy, and two by biopsies only. Twelve patients remain free of disease with a mean follow-up of less than 2 years. The two patients who developed metastases both responded to endocrine ablation by orchiectomy and subsequent adrenalectomy. These data suggest that male breast cancer is highly endocrine sensitive and that endocrine ablation can play an integral part in those men unfortunate enough to develop disseminated disease.

Adrenalectomy↗
PubMed1981

Results of oophorectomy by menstrual and estrogen receptor states in patients with metastatic breast cancer.

The records of 204 women with metastatic breast carcinoma treated by oophorectomy were analyzed. Premenopausal women had a response rate of 50 percent. Forty-one percent of postmenopausal women responded. Those who responded had an average duration of response of 22 months and a length of survival twice that of the nonresponders. There was a better than 60 percent correlation between response to oophorectomy and response to further endocrine ablation. Response to endocrine manipulation is more a function of the hormonal sensitivity of the carcinoma than of menopausal status.

Breast Neoplasms↗
PubMed1980

Cis-platinum therapy of previously treated head and neck cancer: the Southwest Oncology Group's two-dose-per-month outpatient regimen.

The Southwest Oncology Group tested an outpatient Cis-platinum regimen in patients with carcinoma of the head and neck. Courses which consisted to two doses, a week apart, were scheduled to be given at 4-week intervals. Eighty-nine poor risk head and neck cancer patients, who had received extensive prior therapy with surgery, radiation, and/or multiple drugs were studied. Sixteen (18% of all entered and 25% of the 65 fully evaluable) had objective tumor regression. The median duration of response was 136 days. Toxicity was moderate. Myelosuppression was minimal with only 3% of patients exhibiting leukocyte nadirs below 2,000 and less tha 2% experiencing platelet counts below 50,000. Significant, but reversible, impairment of renal function occurred in 8% of patients. Individual susceptibility to such renal toxicity appears to have been predictable. This simple outpatient program with its effectiveness and minimal toxicity in poor risk patients deserves further utilization.

Adult↗
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↗