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Biomedical subjects

D C Tormey

Publications and source records attributed to D C Tormey.

At least 55 records · Page 3Linked to original sources
PubMed1991

A pilot study of three sequential chemotherapeutic regimens in metastatic breast cancer.

The aim of this pilot study was to estimate the toxicity and response rate of an alternating chemotherapeutic program in chemotherapy-naive metastatic breast cancer patients. Treatment consisted of regimen A (given days 1-28): cyclophosphamide 100 mg/m2 PO days 1-14, doxorubicin 30 mg/m2 i.v. days 1 and 8, and 5-fluorouracil 500 mg/m2 i.v. days 1 and 8 (CAF regimen); regimen B (given days 29-56): dibromodulcitol 135 mg/m2 p.o. days 30-39, mitoxantrone 9 mg/m2 i.v. day 29, and vincristine 1.2 mg/m2 i.v. (maximum 2.0 mg) day 29 (DMV regimen); and regimen C (given days 57-84): thiotepa 12 mg/m2, doxorubicin 45 mg/m2 and vinblastine 4.5 mg/m2 all i.v. on day 57. There were 27 eligible patients with a median age of 51 years (range 34-78). On 14 episodes the leukocyte count fell to less than 1 X 10(9)/L during the first six cycles of treatment (14% of 99 cycles). There were no treatment-related deaths. Common non-life-threatening toxicities included thrombocytopenia, anemia, vomiting, and alopecia. Despite having no drugs in common, the leukocyte and platelet nadirs after CAF correlated with the nadir counts after DMV (r values of 0.6829 and 0.5892, respectively; p = 0.01). Among the 23 patients with measurable and/or evaluable disease there were five complete responses (22%) and nine partial responses (39%), with a median time to treatment failure of 29 weeks. The overall median survival was 19 months.

Adult↗
PubMed1991

Phase I study of toremifene in patients with advanced cancer.

A phase I multicenter evaluation of a novel antiestrogen, toremifene, was undertaken in postmenopausal women with various advanced difficult-to-treat malignancies. One hundred and seven women were treated at one of six dosage levels (10, 20, 40, 60, 200, or 400 mg/d orally) for at least 8 weeks. Weekly evaluations for toxicity were conducted. The most common side effects were nausea (31%), vomiting (12%), and hot flashes (29%). Five patients were removed from the study for possible adverse reactions: three patients experienced hypercalcemia; one experienced tremulousness, fatigue, and inability to think clearly; and one had vaginal bleeding. Twelve patients died while on study, 11 with disease progression and one with a pulmonary embolus. Sex hormone-binding globulin (SHBG) levels increased and there was a modest decline in serum antithrombin III levels. Four of 48 assessable patients had partial responses: three with breast cancer and one with endometrial cancer. Toremifene was generally well tolerated at the doses tested.

Adult↗
PubMed1991

Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer.

The records of 2,673 patients randomized according to seven consecutive Eastern Cooperative Oncology Group (ECOG) studies of adjuvant therapy for breast cancer were reviewed for the occurrence of vascular complications. All protocols opened and closed between June 1977 and July 1987. The objectives of the present study were (1) to compare the frequency of vascular complications among patients who received adjuvant therapy for breast cancer with patients on observation, and (2) to estimate the contribution of chemotherapy and hormonal therapy to the occurrence of venous and arterial thrombi. The frequency of thrombosis, both venous and arterial combined, was 5.4% among patients who received adjuvant therapy and was 1.6% among patients on observation (P = .0002). Premenopausal patients who received chemotherapy and tamoxifen had significantly more venous complications than those who received chemotherapy without tamoxifen (2.8% v 0.8%, P = .03). Postmenopausal patients who received tamoxifen and chemotherapy had significantly more venous thrombi than those who received tamoxifen alone (8.0% v 2.3%, P = .03) or those who were observed (8.0% v 0.4%, P less than .0001). Premenopausal patients who received tamoxifen and chemotherapy had a 1.6% frequency of arterial thrombosis, significantly more than patients who received chemotherapy alone (1.6% v 0.0%, P = .004). The frequency of arterial thrombosis among postmenopausal patients was not significantly correlated with adjuvant therapy. In conclusion, patients who received adjuvant therapy for breast cancer had a 5.4% frequency of thromboembolic complications, significantly more than those who were observed. The combination of chemotherapy and tamoxifen was associated with more venous and arterial thromboembolic complications than chemotherapy alone in premenopausal patients and with more venous thrombi than tamoxifen alone among postmenopausal patients.

Aged↗
PubMed1990

Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma.

Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B2) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2). Among the patients with Stage C disease, therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent (P less than 0.0001). The overall death rate was reduced by 33 percent (P approximately 0.006). Treatment with levamisole alone had no detectable effect. The results in the patients with Stage B2 disease were equivocal and too preliminary to allow firm conclusions. Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone--i.e., nausea, vomiting, stomatitis, diarrhea, dermatitis, and leukopenia. These reactions were usually not severe and did not greatly impede patients' compliance with their regimen. We conclude that adjuvant therapy with levamisole and fluorouracil should be standard treatment for Stage C colon carcinoma. Since most patients in our study were treated by community oncologists, this approach should be readily adaptable to conventional medical practice.

Adolescent↗
PubMed1990

Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients. An Eastern Cooperative Oncology Group trial.

The current trial was designed to assess whether the addition of prednisone or prednisone + tamoxifen would enhance the therapeutic effectiveness of 1 year of adjuvant CMF therapy. Premenopausal women with ipsilateral axillary node-positive breast carcinoma and known estrogen receptor (ER) status were randomized to receive 1 year of postoperative treatment with 12 28-day cycles of cyclophosphamide, methotrexate, 5-fluorouracil (CMF), CMF plus prednisone (CMFP), or CMFP plus tamoxifen (CMFPT). There were 553 analyzed cases with 188 receiving CMF, 183 CMFP, and 182 CMFPT. The overall time to relapse (TTR) and survival comparisons between the regimens are not statistically different at a median follow-up time of 7.7 years. The major subgroups currently with a suggestive TTR difference are greater than 3N+ (CMFPT greater than CMF, P = 0.07) and estrogen receptor-negative (ER-) greater than 3N+ (CMFPT greater than CMF, P = 0.03). Patients receiving CMFPT appeared to have a superior survival to CMF in the ER- greater than 3N+ cohort (P = 0.02). The following patient characteristics were associated with a significantly longer TTR: decreasing nodal involvement or tumor size, positive ER status, age greater than or equal to 40 years, and decreasing obesity. The favorable effects of decreasing nodal involvement, positive ER status, age 40 years or greater, and decreasing obesity carried over to survival. Development of amenorrhea was also significantly associated with improved survival (P = 0.001). Toxicity was increased by the addition of prednisone to CMF and by the addition of tamoxifen to CMFP. Overall relapse patterns were similar among the three regimens. The results of the current trial do not currently suggest an overall therapeutic benefit for adding prednisone or only 1 year of tamoxifen to CMF adjuvant treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Phase II study of lonidamine in patients with metastatic breast cancer. An Eastern Cooperative Oncology Group study.

The Eastern Cooperative Oncology Group conducted a phase II study of lonidamine in patients with metastatic breast cancer. The drug was given orally to a maximum daily dose of 340 mg/m2. Forty-two patients were entered on study. One partial response was observed; there were no life-threatening toxicities. The results of this study are compared to two similar phase II trials.

Adult↗
PubMed1990

Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer.

Toremifene is a triphenylethylene derivative structurally and pharmacologically similar to tamoxifen. This Phase I trial assessed the safety, pharmacokinetics, anti-estrogenic, and estrogenic effects of toremifene at six dose levels (10, 20, 40, 60, 200, and 400 mg/day). The most common side-effects associated with therapy included gastrointestinal (nausea/vomiting 43%), anti-estrogenic (hot flashes 29%), and CNS (dizziness/vertigo 12%). Three patients with bone metastases from breast cancer developed hypercalcemia. At doses greater than or equal to 40 mg/day a decline in LH and FSH occurred which was not statistically significant. At all doses tested SHBG rose during therapy. A dose dependent estrogenic blockade was seen on the vaginal epithelium following challenge with transdermal estradiol. Steady-state concentrations of toremifene were reached within 4 weeks, and at doses greater than or equal to 60 mg/day ranged from 879-3445 ng/ml. The half-life was found to be 5 days, and at three weeks following discontinuation of treatment concentrations greater than 24 ng/ml were detected. The N-desmethyl and 4-hydroxy metabolites achieved steady state levels within 4 weeks and had half-lives of 6 and 5 days respectively. Partial responses were seen in 4 patients, 3 with breast cancer treated at 200 mg/day and 1 with endometrial cancer treated at 400 mg/day.

Adult↗
PubMed1990

Tamoxifen metabolites in patients on long-term adjuvant therapy for breast cancer.

Serum concentrations of tamoxifen, 4-OH-tamoxifen, N-desmethyltamoxifen, and metabolites E and Y were assayed to assess the variation of tamoxifen-metabolism during short-term and long-term endocrine treatment for breast cancer. Once steady-state was achieved, serum levels of tamoxifen and its metabolites in individual patients were stable in the short (10 weeks) and long term (over 7 years) (coefficient of variation [CV], 10-15%), but the variation between individuals (CV 50-70%) was high. Serum tamoxifen and N-desmethyltamoxifen levels were not correlated with indices of obesity. Thus this does not explain the large variation between individuals. In addition to the metabolites that were measured, 4-hydroxy-N-desmethyltamoxifen was tentatively identified in patients' serum. Overall, this study demonstrated that the metabolites of tamoxifen are stable (i.e. no metabolic tolerance) for up to 10 years of drug administration.

Breast Neoplasms↗
PubMed1990

Phase II trial of carboplatin in soft-tissue sarcoma.

As part of the Eastern Cooperative Oncology Group program for the assessment of new drugs in sarcomas, a Phase II trial of carboplatin was performed in patients who had received no more than one prior chemotherapy regimen. A total of 50 patients received either 400 mg/m2 or 320 mg/m2 depending on whether they had received prior radiotherapy. A response rate of 16% (95% confidence interval 6-32%) occurred in the 37 patients who had received doxorubicin as their only prior systemic therapy. Three of the six responses were complete and persisted for 7 to 34 months. In contrast none of the 13 patients who received carboplatin after initial progression on doxorubicin and subsequent progression on interferon alpha responded. The overall response rate was therefore 12% (95% confidence interval 5-24%). Toxicity was primarily hematologic, with 14 patients having Eastern Cooperative Oncology Group (ECOG) grade 3 toxicity and no grade 4 or 5 toxicities. In view of the number of complete responses, carboplatin should be studied further in untreated patients with advanced soft tissue sarcoma.

Adult↗
PubMed1990

Adjuvant trial of 12 cycles of CMFPT followed by observation or continuous tamoxifen versus four cycles of CMFPT in postmenopausal women with breast cancer: an Eastern Cooperative Oncology Group phase III study.

A prospectively controlled randomized trial to compare the adjuvant efficacy of 12 cycles of cyclophosphamide, methotrexate, fluorouracil, prednisone, and tamoxifen (CMFPT) followed by observation or a total of 5 years of continuous tamoxifen versus four cycles of CMFPT followed by observation in postmenopausal women with operable node-positive breast cancer was started by the Eastern Cooperative Oncology Group (ECOG) in 1982. In 1986 the study was modified to allow patients on CMFPT X 12 plus continuous tamoxifen to be rerandomized after completing 5 years of tamoxifen to either continue for life or to stop therapy. Patients were stratified for number of involved nodes and estrogen-receptor (ER) status and randomized to receive one of three treatments: CMFPT X 4, CMFPT X 12, or CMFPT X 12 plus continuous tamoxifen. Of 962 patients entered on the study, 803 were eligible. Life-threatening toxicity occurred in 75 and lethal toxicity in seven patients. Median follow-up is 4.1 years; 279 patients had recurrent disease. Time to relapse (TTR) is significantly longer for patients on CMFPT X 12 plus continuous tamoxifen than for CMFPT X 4 (P = .002), or CMFPT X 12 (P = 0.05). Differences between four or 12 cycles of CMFPT are not significant; relapse-free rates at 5 years are 61% for CMFPT X 12 plus continuous tamoxifen, 51% on CMFPT X 12, and 52% on CMFPT X 4. Treatment differences in overall survival are not significant. Hormone receptor status and number of involved nodes were found to be significant prognostic parameters.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Combination chemotherapy of advanced breast cancer. Comparison of dibromodulcitol, doxorubicin, vincristine, and fluoxymesterone to thiotepa, doxorubicin, vinblastine, and fluoxymesterone: an Eastern Cooperative Oncology Group Study.

Two Adriamycin (doxorubicin)-based chemotherapy regimens were investigated in patients with carcinoma of the breast who had failed prior systemic therapy. The two chemotherapy programs, dibromodulcitol, Adriamycin, vincristine, and Halotestin (fluoxymesterone) (DAVH), and thiotepa, Adriamycin, vinblastine, and Halotestin (TAVH), were chosen for comparison on the basis of reported response rates of 40% to 50% with remission durations of 11 months in patients refractory to other cytotoxic chemotherapy. Cycles of DAVH were repeated every 4 weeks. Cycles of TAVH were repeated every 3 weeks. Of 184 patients evaluable for response, 32% of patients treated with DAVH and 38% of patients treated with TAVH had a complete response (CR) or partial response (PR). An additional 5% of patients had nonmeasurable improvement in osseous disease for an overall rate of response (CR + PR + improvement) of 40%. Patients who had previously received cytotoxic chemotherapy for metastatic disease or had early failure after adjuvant therapy had a lower response rate to DAVH, but not to TAVH than those who did not fail prior chemotherapy. Duration of response and survival were similar with the two treatments. There were seven treatment-related deaths, five among patients receiving DAVH and two among patients receiving TAVH. Patients receiving DAVH had significantly more thrombocytopenia and neurologic toxicity than those receiving TAVH. These treatments appear to be reasonable second-line regimens and are good candidates to be used in initial therapy of metastatic disease or adjuvant therapy studies that explore the use of alternating non-cross-resistant combinations with cyclophosphamide, methotrexate, and 5-fluorouracil.

Adenocarcinoma↗
PubMed1989

Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. An intergroup study.

We randomly assigned 536 women who had undergone either a modified radical mastectomy or a total mastectomy with low axillary-node dissection for potentially curable breast carcinoma to receive adjuvant chemotherapy or no-treatment observation. The patients were considered at high risk for recurrence because they had either an estrogen-receptor-negative tumor of any size or an estrogen-receptor-positive tumor at least 3 cm in diameter with no histopathological evidence of axillary-node involvement. The chemotherapy consisted of six four-week cycles of cyclophosphamide (100 mg per square meter of body-surface area orally on days 1 through 14), methotrexate (40 mg per square meter intravenously on days 1 and 8), fluorouracil (600 mg per square meter intravenously on days 1 and 8), and prednisone (40 mg per square meter orally on days 1 through 14). Treatments were balanced with respect to patients' characteristics. The analysis included 406 eligible patients who were entered in the study before October 1, 1987. The overall disease-free survival among patients treated with the four-drug regimen was 84 percent, as compared with 69 percent for the control group, at a median follow-up of three years (P = 0.0001). A treatment benefit was also observed in premenopausal and postmenopausal patients as well as in patients with estrogen-receptor-positive or with estrogen-receptor-negative tumors. Severe or life-threatening hematologic toxicity was encountered in 33 percent of the treated patients, with one death. Our results indicate that adjuvant chemotherapy with six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone is effective in improving three-year disease-free survival among high-risk patients with axillary-node-negative, operable breast cancer. An analysis of the effect of treatment on survival awaits a longer follow-up.

Adult↗
PubMed1989

Cosmesis and local control after irradiation in women treated conservatively for breast cancer.

One hundred twenty-two patients (124 tumor sites) with breast carcinoma (T1 to T3, N0 to N2, M0) were treated by a lumpectomy and radiation therapy at the University of Wisconsin, Madison, from June 1978 to December 1986. Irradiation to the breast and regional lymph nodes was carried out with cobalt 60 teletherapy in 2-Gy fractions to 50 Gy, followed by an additional boost of 10 Gy to the tumorectomy site with coned electrons. Cosmesis was analyzed by scoring the effects of surgery, as well as the effects of irradiation, and by photographic assessment. After a follow-up of 24 to 119 months (median, 36 months), 82% of the patients were found to have good or excellent cosmetic scores. There was a trend that favored better cosmetic results in younger patients and in patients with outer-quadrant lesions. No significant impact of adjuvant chemotherapy on the cosmetic outcome or on the complications of treatment was demonstrated. There were six local recurrences (5.2%), three of which were true recurrences and the other three that were new primary tumors; 11 distant failures (9%) occurred. The following side effects from irradiation developed in only 5 patients (4.1%): match-line fibrosis (n = 2), soft-tissue necrosis (n = 1), and persistent tenderness (n = 2). The conditions of the two patients with persistent tenderness responded favorably with conservative management. We concluded that a lumpectomy, followed by radiation therapy, provides good cosmetic results without compromising the local control rate. If adjuvant chemotherapy is planned, we recommend that it be administered before radiation therapy in favor of concomitant therapy with both modalities.

Adult↗
PubMed1989

Combined modality treatment of local regionally advanced breast cancer patients. 5 to 10 year follow-up.

Local regionally advanced breast cancer carries a poor prognosis overall. There is little published information regarding the long-term follow-up of such patients prospectively treated with surgery, radiation therapy, and early systemic therapy. This communication reports 5-10 year follow-up results on 32 women with local regionally advanced breast cancer prospectively treated with initial surgery followed by systemic chemotherapy and irradiation therapy. Median relapse-free and overall survivals in these women were 37.6 and 62 months, respectively. Nine patients (28%) are currently alive and disease-free 5 to 10 years after diagnosis. Women with inflammatory breast cancer fared as well as other patients with local regionally advanced breast cancer in this small trial. None of 10 patients with gross disease after an initial mastectomy is disease-free as opposed to 9 of 22 women with initially resectable disease (41%). Thus, an appreciable minority of women with resectable local regionally advanced breast cancer may have prolonged disease-free survivals following combined modality therapy.

Actuarial Analysis↗
PubMed1989

Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group.

During the last decade, the Eastern Cooperative Oncology Group (ECOG) has studied a series of combination chemotherapy regimens in metastatic (stage IV) non-small-cell lung cancer (NSCLC). In January 1984, the ECOG activated a randomized study, EST 1583, which concluded the evaluation of combination regimens in phase III trials and initiated the evaluation of single agents exclusively in previously untreated patients. The treatment regimens in EST 1583 consisted of: (1) mitomycin, vinblastine, and cisplatin (MVP); (2) vinblastine and cisplatin (VP); (3) MVP alternating with the regimen cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP); (4) carboplatin followed by the MVP regimen at the time of progression; and (5) iproplatin followed by MVP at the time of progression. From January 1984 to July 1985, 743 patients were entered on this trial and 699 fulfilled the eligibility requirements. The following objective response rates (complete plus partial remissions) were observed: first-line MVP, 20%; VP, 13%; MVP/CAMP, 13%; carboplatin, 9%; iproplatin, 6%; and second-line MVP, 6%. First-line MVP produced a significantly higher response rate than the other treatments (P = .03) adjusted for prognostic variables. Using analyses that were adjusted for prognostic covariates, survival for patients treated on a given regimen was compared with survival for all remaining patients. These analyses showed that treatment with carboplatin was associated with longer survival (median survival time, 31.7 weeks; P = .008) while initial treatment with MVP was associated with a trend for shorter survival (median survival time, 22.7 weeks; P = .09). It should be noted that none of these regimens appear to have produced a clinically meaningful prolongation of survival. Similar analyses evaluating time to progression disclosed that carboplatin-treated patients had a significantly longer time to progression (median time to progression, 29 weeks) than all remaining patients (P = .01). Life-threatening and lethal toxicities (toxicity grades 4 and 5) were greater on the combination regimens than on the single agents (P less than .0001). Based on these results, current group-wide ECOG trials in stage IV NSCLC consist of randomized phase II trials evaluating single agents.

Antineoplastic Combined Chemotherapy Protocols↗