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Biomedical subjects

J Aisner

Publications and source records attributed to J Aisner.

At least 19 recordsLinked to original sources
PubMed1992

Megestrol acetate in cancer anorexia and weight loss.

High-dose megestrol acetate has been associated with increased appetite and weight. To examine the effects of high-dose megestrol acetate in the treatment of anorexia and weight loss in patients with advanced hormone-insensitive malignant lesions, a randomized double-blind placebo-controlled trial was conducted. Patients receiving megestrol acetate for 1 month reported a significant improvement in appetite and adequacy of food intake compared with those receiving placebo. A three-item scale measuring appetite, adequacy of food intake, and concern about weight revealed a higher improvement with megestrol acetate than with placebo. Patients who worsened while receiving placebo had similar favorable changes after the cross over to megestrol acetate. These data indicate that megestrol acetate may improve appetite and food intake in patients with advanced cancer.

Adult↗
PubMed1992

Cisplatin, doxorubicin, cyclophosphamide, and etoposide combination chemotherapy for small-cell lung cancer.

Because of potential synergistic interactions, we added 25 mg/m2 i.v. cisplatin (P) 25 given on days 1-5 to the combination of 45 mg/m2 i.v. doxorubicin (A) given on day 1, 800 mg/m2 i.v. cyclophosphamide (C) given on day 1, and 50 mg/m2 i.v. etoposide (E) given on days 1-5. The resulting PACE regimen was given every 21 days for the first three courses and then every 28 days for the next five courses. PACE was used in two trials: the first, for both limited and extensive disease, was conducted at the University of Maryland Cancer Center and North Shore University Hospital; and the second, for extensive disease, was carried out as a Cancer and Leukemia Group B pilot study. Chest irradiation was not used. Prophylactic cranial irradiation at a dose of 3,000 cGy was given to all patients achieving a complete response (CR). A total of 33 subjects were entered in the first study; 8 of the 15 (53%) presenting with limited disease and 7 of the 18 (39%) exhibiting extensive disease achieved a CR. A partial response (PR) was obtained in 27% and 33% of cases, respectively. Of the 34 patients entered in the second study, 25 were eligible; 8 (32%) achieved a CR and 6 (24%) showed a PR. Toxicity was severe in both studies, including greater than 90% severe or life-threatening leukopenia and thrombocytopenia. Serial creatinine-clearance evaluations in the first study indicated progressive deterioration, which required discontinuation of the cisplatin before the planned completion of treatment in most cases. Since the response rate was no higher than the historic data reported for the three-drug ACE combination and because the toxicity was severe, the studies were stopped and patients were followed for survival. After a follow-up period of greater than 6 years, the median survival was 24 months for limited disease, with 33% and 27% of the patients being alive at 3 and 6.5 years, respectively. The median survival for extensive disease was 15 and 11 months in the first and second studies, respectively. These pilot studies suggest that the addition of cisplatin may augment the activity of the ACE regimen, but at the cost of severe toxicity. Further studies seem warranted if the myelotoxicity can be better controlled.

Adult↗
PubMed1992

Combined-modality therapies for non-small cell lung cancer.

Regionally advanced stage III non-small cell lung cancer (NSCLC) accounts for nearly 40% of all presentations of NSCLC. In the past, such patients received radiotherapy alone, but the median and long-term survival durations were disappointingly poor. Past attempts at combining chemotherapy and radiation were also disappointing, and were troubled by low doses of radiation or orthovoltage equipment or both. Recently, cisplatin-containing regimens have shown some efficacy in stage IV disease. The response rate for these combinations in stage III disease is nearly double that in stage IV disease. The greater response in stage III has led to a series of trials of sequenced chemotherapy and radiotherapy for treatment of regionally advanced (unresectable stage IIIA and IIIB) NSCLC. Several randomized trials have now shown a statistically significant advantage for the combined modality over radiation alone regarding time to treatment failure, median survival duration, and percent of long-term survivors. Other trials have focused on the concurrent use of chemotherapy and radiotherapy. Several pilot studies have suggested that concurrent cisplatin plus chest irradiation can produce apparently beneficial results with respect to local control and are the subject of ongoing clinical trials. At the University of Maryland Cancer Center, we have combined weekly carboplatin 100 mg/m2 with concurrent chest irradiation. The preliminary results are very encouraging. The toxicity of this treatment program is very manageable, and preliminary data suggest excellent local control and survival. Other pilot studies have suggested that combination chemotherapy with concurrent radiotherapy is also technically feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Potential applications of high-dose megestrol acetate in breast cancer.

Empiric clinical trials have revealed new mechanisms by which hormonal therapies may exert their antitumor effects. Initial studies using escalated doses of agents like toremifene and megestrol acetate have yielded interesting results, showing responses in hormone-receptor-negative patients and in patients progressing after standard doses, respectively. A trial by Cancer and Leukemia Group B randomizing patients with advanced breast cancer to standard-dose (160 mg) megestrol acetate or to 5 or 10 times the standard dose (800 and 1,600 mg) has completed accrual. It is hoped that these results will provide a definitive answer to the dose-response issue for breast cancer. However, regardless of this trial's ultimate outcome, higher doses of megestrol acetate have demonstrated important new effects on appetite stimulation and weight gain; ongoing laboratory research promises potential roles for megestrol acetate in the reversal of chemotherapeutic drug-induced tumor resistance.

Adult↗
PubMed1992

Intensive combination chemotherapy, concurrent chest irradiation, and warfarin for the treatment of limited-disease small-cell lung cancer: a Cancer and Leukemia Group B pilot study.

PURPOSE: In prior Cancer and Leukemia Group B (CALGB) studies, combined chemotherapy and thoracic irradiation was superior to chemotherapy alone in limited-disease (LD) small-cell lung cancer (SCLC). A combined modality pilot study was performed to test the feasibility of adding warfarin to aggressive chemoradiotherapy for LD SCLC. PATIENTS AND METHODS: Combination chemotherapy with doxorubicin 45 mg/m2 intravenously (IV) on day 1, cyclophosphamide 800 mg/m2 IV on day 1, and etoposide (ACE) 80 mg/m2 on days 1 to 3 was given every 21 days for the first three courses. The fourth and fifth courses substituted cisplatin 33 mg/m2 IV on days 1 to 3 for the doxorubicin, with concurrent chest irradiation to a total of 4,000 cGy given in 20 fractions during a 4-week period followed by a boost of 1,000 cGy in five fractions during a 1-week period. Prophylactic cranial irradiation, 3,000 cGy was given concurrently in 10 fractions during a 2-week period. Courses 6 to 8 again used ACE chemotherapy, but courses 4 to 8 were given on a 28-day schedule with dose adjustment for hematologic or renal toxicity. Warfarin was given throughout the treatment period titrated to achieve a prothrombin time (PT) of 1.5 to 2 times the control. Patients with histologically proven limited-stage SCLC, good performance status, and normal renal, hematologic, and hepatic functions were eligible. RESULTS: Sixty-one of 66 patients entered onto the study were eligible and assessable. Fifty-four (89%) (95%) confidence interval [CI], 78% to 95%) experienced an objective response, 35 (57%) achieved a complete response (CR) (95% CI, 44% to 70%), and 17 (28%) achieved a partial response (95% CI, 16% to 39%). Median durations were CR, 26.3 months; failure-free survival, 11.8 months; and survival, 18 months. Forty-one percent of the patients were alive at 2 years, 33% were alive at 3 years, and 25% were alive at 4 or more years. Median follow-up for survivors is 5 years (range, 3.5 to 5.9 years). Severe or life-threatening myelosuppression occurred in 90%, infection occurred in 34%, fever without documented infection occurred in 26%, and pulmonary toxicity occurred in 6%. Another 6% of patients experienced severe or life-threatening hemorrhages. There were four treatment-related fatalities. The pulmonary toxicities have been associated with the resumption of ACE chemotherapy after chest irradiation. CONCLUSIONS: These highly encouraging response and survival results compare favorably with any prior CALGB group study. Although they are somewhat more toxic, they are comparable to the best published results. A randomized study that examines the role of warfarin is underway.

Adult↗
PubMed1992

Treatment of limited-disease small cell lung cancer.

Refinements in the use of chemotherapy, both alone and in combination with chest irradiation, have prolonged the survival of patients with limited-disease small cell lung cancer in the last two decades. Based on reviews of trials of patients with both limited and extensive disease, these improvements appear to transcend adjustments made in the staging of limited disease. Alternation of chemotherapy regimens according to the Goldie-Coldman hypothesis has not proven advantageous in this setting. Etoposide combined with cisplatin has been effective as a salvage regimen for previously treated small cell lung cancer, and is particularly useful in first-line treatment approaches when given concurrently with chest irradiation. Although prophylactic cranial irradiation has reduced central nervous system recurrence in complete responders, its role remains controversial due to an unclear effect on survival and associated long-term toxicities. Our present understanding of the biology of limited-disease small cell lung cancer should lead to further refinements in treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Carboplatin in the treatment of squamous cell head and neck cancers.

Cancer of the head and neck, or aerodigestive tract, represents only a small percentage of all cancer cases in the United States, yet its variable presentations have wide-ranging implications that make it one of the most problematic cancers. Recent research has focused on treatment approaches for the patient with advanced disease. Encouraging results have been noted with combination cisplatin/5-fluorouracil (5-FU) and, more recently, with carboplatin/5-FU, particularly in previously untreated patients. The carboplatin-containing regimen has several important advantages over that with cisplatin, including outpatient administration and less severe nausea and vomiting, an important consideration in terms of nutritional support for head and neck cancer patients. The demonstration of possible synergistic activity between platinum compounds and radiation therapy also has prompted considerable interest, as such a combined-modality approach offers the potential for improved quality of life in patients with head and neck cancers. Carboplatin is an excellent agent for the treatment of squamous cell head and neck cancers, with recognized single-agent activity and a high degree of efficacy, when combined with 5-FU. Carboplatin can be combined effectively with concurrent radiotherapy and, with its advantages over cisplatin, is increasingly used as part of initial therapy for head and neck cancers.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Phase I/II study of cyclophosphamide, doxorubicin, fluorouracil, and leucovorin for treatment of metastatic adenocarcinoma.

Leucovorin enhances the cytotoxicity of fluorouracil (5-FU) in patients with colorectal cancer and may increase the efficacy of combination chemotherapy regimens containing 5-FU. To determine the maximum tolerated dose of 5-FU with leucovorin for use in combination with cyclophosphamide and doxorubicin, we conducted a phase I/II trial in 20 patients. The doses of leucovorin (200 mg/m2 on days 1-5), cyclophosphamide (500 mg/m2 on day 1), and doxorubicin (40 mg/m2 on day 1) were held constant, while the dose of 5-FU was escalated in cohorts of patients beginning at 150 mg/m2 on days 1-5. Cycles were repeated every 3 weeks. Significant mucositis, diarrhea, and myelosuppression were infrequently observed in patients receiving up to 250 mg/m2 5-FU on days 1-5. In contrast, at a dose of 300 mg/m2 on days 1-5, three of six patients had granulocyte count nadirs of less than 500/microL during the first cycle of therapy, and two of these three had platelet counts of less than 25,000/microL. In addition, two patients treated at this dose had significant mucosal toxic effects, and three had insufficient recovery to permit a second course by day 22. Among 14 patients with assessable breast cancer, there were one complete and nine partial responses (response rate 71%). Leucovorin modulation of 5-FU can be safely incorporated into combination chemotherapy with cyclophosphamide and doxorubicin and provides a highly active regimen for treatment of metastatic breast cancer. Further study will be required to determine whether the addition of leucovorin significantly enhances the activity of this regimen.

Adenocarcinoma↗
PubMed1991

Etoposide. Current and future status.

Etoposide (VP-16-213) is an antineoplastic agent with demonstrated efficacy against a broad spectrum of human malignancies, including testicular, germ cell, lung, and other cancers. Etoposide can be synergistic with other agents. As part of combination chemotherapy, etoposide has become a so-called standard in therapies for testicular cancer and small cell lung cancer. Its activity in tumors such as lymphoma and leukemia, as well as solid tumors, identifies etoposide as a highly important chemotherapeutic agent. Cellular and animal models have shown that the cell kill and tumor response depend on both dose and time of exposure. Recent clinical studies again show that dose and schedule of etoposide can have important effects on clinical response to the drug. Further research should now continue: (1) on the use of etoposide as part of initial therapy in several cancers, and (2) in higher doses and prolonged schedules to optimize this agent's potential.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A phase I/II study of high-dose megestrol acetate in the treatment of metastatic breast cancer.

A dose-response relationship has been suggested for medroxyprogesterone acetate in the treatment of advanced breast cancer. To determine the tolerability and efficacy of increasing doses of megestrol acetate in the treatment of metastatic breast cancer, we conducted a phase I/II study among 57 patients. Three patients each received 480, 800, and 1280 mg/d; 48 patients received 1600 mg/d. Of the 57 patients, 56 patients had had disease progression on prior hormone therapy, chemotherapy, or both. Twenty-seven patients had previously received standard-dose MA (160 mg/d). Among the 37 patients with measurable disease, high-dose megestrol acetate (HDMA) produced 6 (16%) complete responses (CRs) and 6 (16%) partial responses (PRs); 11 patients achieved stable disease (SD). HDMA resulted in improvement or stabilization in 12 of the 20 patients with evaluable, non-measurable disease. There were no responses among the 6 patients with liver metastases. Among the 27 patients who were previously treated with standard-dose MA, including 9 patients with primary treatment failure, HDMA resulted in 1 CR, 3 PRs, and 10 SD. Toxicities, which were mild and reversible, included fluid retention, hypertension, hyperglycemia, and mild congestive heart failure. Two patients had superficial phlebitis. The most profound side effect was weight gain which occurred in 43 patients (75%). This study suggests a dose-response relationship for MA in the treatment of advanced breast cancer. A randomized trial to determine the optimal dose is ongoing.

Adult↗
PubMed1991

Long-term results of a combined modality approach in treating inflammatory carcinoma of the breast.

Twenty-eight patients with inflammatory carcinoma of the breast were managed initially by induction chemotherapy consisting of 3 courses of a combination of cyclophosphamide, doxorubicin hydrochloride, and 5-fluorouracil. Twenty-two showed a partial response, and 21 underwent mastectomies. Histopathologic examination of the surgical specimens revealed no residual tumor in 2 breasts, but all 21 patients had residual metastases in their axillary lymph nodes. Postoperatively, they received the same chemotherapy. The other six patients who failed to respond to induction chemotherapy received radical radiation therapy followed by a combination chemotherapy regimen that consisted of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone. Any patient in whom chemotherapy failed during the follow-up period was treated by radiation therapy and/or a combination of mitomycin-C and vinblastine as necessary. At the time of diagnosis, 17 patients who had no evidence of distant metastasis, i.e., stage III B disease, had disease-free survival ranging from 5 to more than 84 months, with a median of 30 months, and an overall survival of 7 to more than 120 months with a median of 32 months. The 5-year survival rate was 18%. The other 11 patients who had distant metastases, i.e., stage IV disease, had an overall survival ranging from 4 to 14 months. The results of this approach of initial systemic chemotherapy followed by local-regional cytoreductive therapy, then systemic therapy, might suggest some survival benefits in patients with stage III disease.

Adult↗
PubMed1990

Carboplatin in malignant mesothelioma: a phase II study of the Cancer and Leukemia Group B.

Carboplatin (400 mg/m2) was given at 28-day intervals to 41 patients with malignant mesothelioma. In all, 40 patients were eligible and evaluable for response. Partial responses were seen in 2 cases (5%); regression of evaluable disease, in 1 patient (2%); and stable disease, in 19 subjects (48%). A median of two doses of carboplatin per patient resulted in mild toxicity. Leukopenia (less than or equal to 2,000 cells/microliters) and thrombocytopenia (less than 100,000 cells/microliters) were seen in only 6% and 20% of the patients, respectively. Median survival from study entry was estimated at 7.1 months, with a 1-year survival of 25% +/- 7%. Carboplatin given at a dose of 400 mg/m2 at 28-day intervals shows minor activity against malignant mesothelioma.

Adult↗
PubMed1990

Small bowel obstruction as a late complication of the treatment of Hodgkin's disease.

Small bowel obstruction (SBO) as a late complication of the treatment of Hodgkin's disease was found in 32 of 398 (8%) patients followed over a 20 year period. The vast majority of these patients had an initial staging laparotomy as part of staging protocols. Of 51 obstructive episodes, 13 were diagnosed clinically, 12 of the 13 had prior radiological or surgical documentation. Thirty-one episodes were shown radiologically; four were demonstrated at laparotomy and three recurrent episodes were identified in an unspecified manner. The median duration of each episode was 3 days and the median time between commencement from treatment for Hodgkin's disease and the development of a SBO was 21 months. Thirty-one of the 32 patients had had a staging laparotomy or prior abdominal surgery. Two patients had SBO because of non-Hodgkin's lymphoma and one had SBO secondary to short bowel syndrome. These are thus not true complications of disease treatment. Twenty-nine of the 32 or 7.2% of patients thus had possible treatment-related SBO. The cause of SBO was recorded as adhesions from previous surgery in 27 of the 51 episodes. This was confirmed at laparotomy in 16 patients. Twenty-five of the 32 patients had received abdominal irradiation but only three obstructive episodes were attributed to radiation enteritis and fibrosis. In one of 22 patients who received chemotherapy, Vinblastine was implicated as a cause for SBO. Eighteen patients required laparotomy to lyse adhesions while the others were treated conservatively with tube drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

A feasibility study of intensive CAF as outpatient adjuvant therapy for stage II breast cancer in a cooperative group: CALGB 8443.

In preparation for a national Phase III study of dose and dose intensity in the treatment of node-positive, Stage II adenocarcinoma of the female breast, CALGB instituted a pilot study of intensive intravenous outpatient CAF (cyclophosphamide, Adriamycin, 5-fluorouracil) for four months. This study was designed to give full doses of drugs without dose reduction for hematologic toxicity. In order to evaluate the feasibility of physician and patient compliance with a potentially toxic therapy, a multi-institution pilot study was performed. This protocol demonstrated that a cooperative group could deliver toxic drug doses to outpatients with a median of 98% of cyclophosphamide, 97% of Adriamycin (doxorubicin), and 91% of 5-fluorouracil administered on schedule. Major side effects, as expected, were leukopenia, nausea, and vomiting. Disease-free survival is at least equivalent to that observed in previous studies.

Adenocarcinoma↗
PubMed1990

Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) regimen for adults with advanced sarcoma.

The mesna, doxorubicin, ifosfamide, dacarbazine regimen produced a 47% response rate (including 10% complete responses) in 105 eligible adults with advanced sarcoma. The major dose-limiting toxicity was granulocytopenia. There was one toxic death from sepsis. Central nervous system and renal toxicity occurred infrequently, perhaps as a result of the continuous-infusion schedule. This regimen is being evaluated further in advanced disease, the adjuvant setting, and in combination with bone marrow colony-stimulating factors.

Adult↗
PubMed1990

Treatment of cancer anorexia with megestrol acetate: impact on quality of life.

The quality of life of patients with advanced cancer depends to a large degree on the presence of disease or treatment-related symptoms. Anorexia is frequent in cancer patients, but has received less attention than other symptoms such as pain or nausea. Yet, anorexia is important because it reduces caloric intake and leads to malnutrition. Further, lack of appetite can disrupt basic activities of daily living, such as eating, and may also interfere with family and social interactions. To test the efficacy of drugs that reverse anorexia, we need accurate and reliable parameters to quantitate this symptom. The effects of anorexia and its reversal on the patients' clinical progress, food intake, nutritional status, and quality of life need to be evaluated. Our ongoing studies demonstrate that megestrol acetate can reverse cancer anorexia and that appetite changes strongly correlate with changes in weight, food intake, and quality of life scores.

Anorexia↗
PubMed1990

Current status of high-dose progestins in breast cancer.

Progestins at standard doses have compared favorably with tamoxifen for the front-line treatment of women with metastatic breast cancer. Attempts to further enhance the role of progestins have centered on dosage escalation, based on European data suggesting a dose-response effect. A phase I/II pilot trial at the University of Maryland demonstrated that doses of megestrol acetate up to 1,600 mg/d were well tolerated for prolonged periods. Responses were seen in patients whose disease was refractory to both standard doses of megestrol acetate and to tamoxifen. Different mechanisms of progestin action on breast tumors are theorized at the higher doses, which could account for the dose-response effect. Two large multi-institutional dose comparison trials of megestrol acetate in metastatic breast cancer have been undertaken in the United States. The Piedmont Oncology Association recently reported a significant benefit for megestrol acetate 800 mg/d compared with the standard 160 mg/d in terms of response and disease-free and overall survival. The largest trial is currently ongoing in the Cancer and Leukemia Group B. They are comparing 800 and 1,600 mg/d with standard doses, and results from this study are eagerly anticipated.

Antineoplastic Agents↗