[Show abstract][Hide abstract] ABSTRACT: Despite the utility of newer antidepressants for alleviating hot flashes, antidepressants do not work adequately enough in many patients. Gabapentin is a nonhormonal agent that also can reduce hot flashes. No data have been available to address whether the combination of both agents would more effectively alleviate hot flashes, compared with gabapentin alone, in patients with inadequate hot flash control with an antidepressant alone.
This was a randomized trial in which 118 patients with inadequate hot flash control on an antidepressant were randomly assigned to receive both an antidepressant and gabapentin versus being weaned off the antidepressant and receiving gabapentin alone. Patients were observed for 5 weeks (including a baseline week in which patients continued on their current antidepressant without gabapentin) during which time they completed validated daily hot flash diaries.
Ninety-one patients provided complete data at the 5-week assessment. Regardless of whether or not the antidepressant was continued when gabapentin was started, there was an approximately 50% median reduction in hot flash frequencies (54%; 95% CI, 34% to 70% for combined treatment v 49%; 95% CI, 26% to 58% for gabapentin alone) and scores (56%; 95% CI, 26% to 71% for combined treatment v 60%; 95% CI, 33% to 73% for gabapentin alone).
Gabapentin seems to decrease hot flashes by approximately 50% in women with inadequate hot flash control who were using an antidepressant. This study saw no significant additional hot flash reduction from continuation of the antidepressant.
Preview · Article · Feb 2007 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: The North Central Cancer Treatment Group Phase III trial compared efficacy of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with doxorubicin plus cisplatin (AC) for patients with advanced endometrial cancer.
Twenty-eight patients were randomly assigned to treatment with doxorubicin 30 mg/m2 + cisplatin 70 mg/m2 IV q 4 weeks vs. methotrexate 30 mg/m2 IV days 1, 15, and 22, vinblastine 3 mg/m2 IV days 2, 15, and 22, doxorubicin 30 mg/m2 IV day 2, and cisplatin 70 mg/m2 day 2 of a 4-week cycle. The trial was terminated prematurely due to slow accrual.
Prior to early closure of the protocol, there were 15 patients entered on the AC regimen and 13 to the MVAC regimen. There were 3 PR (20%) for AC and 3 CR (23%) and 3 PR (23%) for MVAC. Median PFS was 4.0 months for AC and 6.9 months for MVAC. Median survival was 13.2 months for AC and 16.8 months for MVAC. Toxicity was substantial for MVAC vs. AC with severe leukopenia seen in 69% vs. 33% of patients and severe thrombocytopenia 23% vs. 0%. No treatment-related deaths were seen.
MVAC and AC are active regimens in the treatment of advanced/recurrent or metastatic endometrial cancer. The premature closure of the protocol resulted in small patient numbers that left the protocol underpowered to address the primary objective of demonstrating improved CR rate for MVAC over AC. MVAC has substantial toxicity compared to AC and is not substantially superior to AC. MVAC cannot be considered as a standard for treatment in this patient population.
No preview · Article · Apr 2006 · Gynecologic Oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose: We performed a randomized trial to comparesurvival distributions and toxicity of radiation therapy (RT)and DBD with RT and BCNU in patientswith high-grade astrocytoma. Methods: A total of 238patients with supratentorial grade 3 and grade 4astrocytoma were studied. Patients were stratified by age,extent of surgery, tumor grade, and performance scoreand randomly assigned to receive RT 55-60 Gyand either DBD, 200 mg/m2 orally on Days1–10 every five weeks or BCNU, 200 mg/m2intravenously every seven weeks. Median age was 60years; 62% were 55 years or older. Eighty-threepercent had subtotal resection, 58% had grade 4tumors, and 83% had performance scores of 0–2.Results: Survival distributions for all patients in thetwo arms were similar, with median survival of41 weeks in each arm. Time to progressiondistributions were virtually identical, with medians of 22weeks. BCNU produced significantly greater hematologic toxicity; medianleukocyte and platelet nadirs on the first cyclewere 3.6 vs. 4.7 (P=0.0001) and117 vs. 162 (P < 0.0001),="" and="" overallplatelet="" nadirs="" were="" 80.5="" vs.="" 114="" (p="0.0019)." non-hematologic="" toxicities="" were="" also="" significantly="" greater="" withbcnu,="" including="" nausea="" (57%="" vs.="" 31%;="" p="">
No preview · Article · Jun 1997 · Journal of Neuro-Oncology
[Show abstract][Hide abstract] ABSTRACT: Thirty-nine women with advanced, recurrent epithelial ovarian carcinoma who failed prior treatment with a platinum-based regimen were treated with leucovorin, 20 mg/m2 intravenously followed by 5-fluorouracil, 425 mg/m2 intravenously, daily for 5 consecutive days every 5 weeks in a phase II trial. Partial regressions were seen in 3 of 15 (20%) measurable disease patients, and objective regressions were seen in 3 of 14 (21%) evaluable/nonmeasurable disease patients. A 50% or greater decrease in CA-125 level was observed in 3 of 10 (30%) patients with no objectively evaluable or measurable disease. Overall objective response rate was 23% (95% confidence interval: 11 to 39%) in all 39 patients evaluated, with a median time to progression of 3 months and overall median survival of 7 months. Toxicities were acceptable and consisted of neutropenia, thrombocytopenia, stomatitis, and mild diarrhea. 5-Fluorouracil, as administered in this protocol, had modest antitumor activity in cisplatin-refractory ovarian carcinoma of short duration and minimal toxicity.
No preview · Article · Sep 1994 · Gynecologic Oncology
[Show abstract][Hide abstract] ABSTRACT: Vasomotor hot flashes are a common symptom in women during menopause and in men who have undergone androgen-deprivation therapy for prostate cancer. Although treatment with estrogens in women and androgens in men can attenuate these symptoms, these hormones may be contraindicated in women with breast cancer and in men with prostate cancer. Pilot trials have suggested that the progestational agent megestrol acetate can ameliorate hot flashes in both groups of patients.
The patients included 97 women with a history of breast cancer and 66 men with prostate cancer who had undergone androgen-deprivation therapy. All patients had experienced bothersome hot flashes (median number per day at base line, 6.1 for the women and 8.4 for the men). After a one-week pretreatment observation period, the patients received megestrol acetate (20 mg twice daily) for four weeks, followed by placebo for four weeks, or vice versa in a double-blind manner as determined by pretreatment randomization. The patients documented the frequency and severity of hot flashes in daily symptom diaries.
After four weeks, hot flashes were reduced by 21 percent in the group receiving placebo first and by 85 percent in the group receiving megestrol acetate first (P < 0.001). An intention-to-treat analysis of data for all eligible treated patients showed that 74 percent of the megestrol acetate group, as compared with 20 percent of the placebo group, had a decrease of 50 percent or more in the frequency of hot flashes during the first four weeks (P < 0.001). The degree of efficacy was similar in men and women. The only side effect was withdrawal menstrual bleeding in women, generally occurring one to two weeks after the megestrol acetate had been discontinued.
Low-dose megestrol acetate is well tolerated and can substantially decrease the frequency of hot flashes in women and men.
No preview · Article · Sep 1994 · New England Journal of Medicine
[Show abstract][Hide abstract] ABSTRACT: This study was developed to determine whether descriptive information from a patient-completed questionnaire could provide prognostic information that was independent from that already obtained by the patient's physician.
An initial detailed questionnaire was administered to approximately 150 patients with advanced cancer. This questionnaire was subsequently revised and given to a total of 1,115 patients with advanced colorectal or lung cancer. Univariate and multivariate analyses were performed to evaluate the data from these questionnaires.
A total of 36 variables showed statistically significant prognostic information for survival in univariate analyses, even though many of these variables were associated with only a minimal increase in risk. A multivariate analysis demonstrated that there was a high correlation between many variables. Three major groups of variables became apparent as providing strong prognostic information. These included the following: (1) a physician's assessment of performance status (PS); (2) a patient's assessment of their own PS; and (3) a nutritional factor such as appetite, caloric intake, or overall food intake.
Data generated by a patient-completed questionnaire can provide important prognostic information independent from that obtained by other physician-determined prognostic factors.
[Show abstract][Hide abstract] ABSTRACT: To compare the survival of patients with medically inoperable or unresectable stage III non-small cell lung cancer treated with thoracic radiotherapy alone or in combination with chemotherapy.
Randomized, prospective phase III trial.
Multi-institutional cooperative oncology group.
A total of 121 patients were enrolled in the study, of whom 7 (5.8%) were ineligible. All patients were ambulatory and had measurable or evaluable disease. Before they were randomized, patients were stratified by ECOG performance score, histologic type, maximum tumor diameter, and NCCTG institution.
Radiotherapy consisted of a total of 5000 cGy in 5 weeks with a 1000 cGy boost in 5 fractions to a small tumor field. Combined modality therapy was MACC which is intravenous methotrexate, intravenous doxorubicin, intravenous cyclophosphamide, and oral lomustine (CCNU), on day 1 and 28. Chemotherapy was followed by identical thoracic radiotherapy 4 weeks after the second cycle of chemotherapy. Four weeks after thoracic radiotherapy was completed, patients received another two cycles of identical chemotherapy. Patients who had progression of disease after chest irradiation only were treated with MACC chemotherapy.
Major clinical responses were observed in 31 of 56 (55%; 95% Cl, 42% to 68%) patients treated with combination therapy and 37 of 58 (64%; Cl, 51% to 76%) treated with radiation only (P greater than 0.2). The median time to progression was 192 days with radiotherapy only compared with 199 days for combined modality therapy (P greater than 0.2). The median survival time was 313 days compared with 317 days, respectively (P greater than 0.2). The 1-, 2-, and 5-year survival rates after thoracic radiation only were 45% (Cl, 32% to 58%), 16% (Cl, 6% to 25%), and 7%. With chemoradiotherapy, the survival rates were 46% (Cl, 33% to 60%), 21% (Cl, 11% to 32%), and 5%, respectively. Myelosuppression was significantly greater for the combined modality therapy arm (P = 0.002).
Chemotherapy with MACC, in combination with thoracic radiotherapy, did not result in significant survival advantage compared with radiation alone (P greater than 0.2) in patients with medically inoperable or unresectable stage III non-small cell lung cancer.
No preview · Article · Dec 1991 · Annals of internal medicine
[Show abstract][Hide abstract] ABSTRACT: A prospective clinical trial was done to evaluate the efficacy and toxicity of cisplatin plus etoposide (VP-16) in patients with breast cancer who failed one previous chemotherapy regimen for advanced disease or relapsed within 12 months of adjuvant chemotherapy. Partial responses occurred in 11 of 44 evaluable patients (25%; 95% confidence interval (CI), 13% to 40%). The median time to disease progression in responding patients was 4 months (range, 3 to 6+ months), whereas the median time to disease progression and survival for all patients who were treated were 3 and 7 months, respectively. There was marked toxicity related to this protocol treatment including pancytopenia, gastrointestinal upset, and renal insufficiency. Two treatment-related deaths occurred; one from sepsis and one from renal failure. Thus, this regimen, as second-line chemotherapy for women with metastatic breast cancer, resulted in moderate, short-term, antitumor activity at the expense of marked toxicity.