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J Aisner

Publications and source records attributed to J Aisner.

At least 37 records · Page 2Linked to original sources
PubMed1996

Paclitaxel and carboplatin in metastatic non-small cell lung cancer: preliminary results of a phase I study.

Given their known activity against non-small cell lung cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin were combined in this phase I study of patients with metastatic disease to determine the maximum tolerated dose and the dose-limiting toxicity of the combination. The initial dose of paclitaxel was fixed at 135 mg/m2 given as a 24-hour infusion with carboplatin administered in escalating doses in cohorts using Calvert's formula-dose (mg) = target AUC x (GFR + 25), where AUC is area under the concentration-time curve and GFR is glomerular filtration rate-based on target AUCs of 5, 7, 9, or 11 mg/mL.min. Dose escalations were based on cycle 1 toxicities. Filgrastim was not administered with the first cycle until two or more patients developed grade 4 or febrile neutropenia at the preceding dose level. Dose-limiting toxicity occurred in two patients at level 2 (cycle 1), and filgrastim was administered thereafter for the next four dose levels. Grade 4 thrombocytopenia was seen at level 4; thus, the carboplatin dose was de-escalated thereafter, and the paclitaxel dose escalated. Rare nonhematologic toxicities include fatigue, diarrhea, and nausea and vomiting. Among the first 30 patients, one had a complete response and 14 had partial responses, for an overall response rate of 50%. The combination of paclitaxel and carboplatin is active in non-small cell lung cancer, and the recommended phase II dose without filgrastim support is paclitaxel 175 mg/m2 via a 24-hour infusion with the carboplatin dose targeted to achieve an AUC of 7 mg/ mL.min.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease.

Based on superior results observed with combined-modality therapy over radiotherapy alone and on the authors' previous work with carboplatin and standard daily thoracic radiotherapy in patients with advanced, unresectable non-small cell lung cancer, a phase II study was designed to incorporate radiosensitizing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into the carboplatin/radiotherapy regimen, to improve the therapeutic index and define the toxicities. Thirty-two patients have been entered. Paclitaxel 45 mg/m2/wk was administered over 3 hours prior to carboplatin (100 mg/m2/wk) and thoracic radiotherapy (1.8 Gy/d 5 days a week; total dose, 60 to 65 Gy). No grade 4 toxicities occurred. Seven patients had chemotherapy doses delayed because of grade 3 neutropenia, and one patient had grade 3 mucositis/esophagitis that required hospitalization. Median survival has not yet been reached, and all patients are being followed. These preliminary data demonstrate the feasibility of combined concurrent chemoradiotherapy, with acceptable toxicities. Further investigation is needed to optimize carboplatin dosage with adaptive control using formulas based on pharmacokinetics and pharmacodynamics. Full-dose induction chemotherapy regimens to maximize the systemic effects of chemotherapy should precede concurrent chemoradiotherapy in future studies.

Adult↗
PubMed1995

Combination chemotherapy for metastatic or recurrent carcinoma of the breast--a randomized phase III trial comparing CAF versus VATH versus VATH alternating with CMFVP: Cancer and Leukemia Group B Study 8281.

PURPOSE: We sought to compare three doxorubicin-based therapies for metastatic breast cancer for response frequency, time to treatment failure (TTF), and survival. MATERIALS AND METHODS: Women with metastatic breast cancer who had measurable disease, required laboratory tests, had received no prior chemotherapy for metastases, had a Cancer and Leukemia Group B (CALGB) performance status < or = 2, and provided informed consent were eligible. Treatment included the following: arm I--cyclophosphamide, doxorubicin, and fluorouracil (CAF); arm II--vinblastine, doxorubicin, thiotepa, and halotestin (VATH); and arm III--VATH alternating with cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) on cycles 3, 5, 7, 9, etc. Doses were modified for toxicities. Standard CALGB response and toxicity criteria were used. RESULTS: Between August 1982 and February 1987, 497 women were entered and 491 were treated on study. Pretreatment characteristics were well balanced and the median follow-up duration was 79 months. There were no significant differences in response (complete [CR] plus partial [PR]) at 50% on arm I, 57% on arm II, and 51% on arm III. The median TTFs were 8, 8, and 9 months, respectively, in favor of arm III when compared with arm I (P = .028). The median survival times for treatment arms I, II, and III were 15, 17, and 17 months, respectively. After multivariate regression analyses, only estrogen receptors (ER), performance status, and number of metastatic sites influenced TTF and survival. Leukopenia was the most common grade 3 or 4 toxicity, occurring in 90%, 80%, and 92% of patients per arm, respectively. Lethal toxicities were seen in four, five, and six women, respectively. Overall, there were more grade > or = 3 toxicities on arm II than I, and most occurred on arm III (P = .02). CONCLUSION: The VATH regimen appears similarly effective to the CAF regimen as initial therapy. Alternating CMFVP with VATH did not improve response rate or survival. After accounting for other variables, treatment arm was not related to outcome. New therapeutic regimens are still needed.

Adult↗
PubMed1995

Current approach to malignant mesothelioma of the pleura.

Malignant mesothelioma of the pleura occurs primarily in individuals who were exposed to asbestos either in the workplace or home. The incidence of malignant mesothelioma is rising and, reflective of the malignancy's long latency period, is expected to continue to increase into the next century. Current treatment measures, including surgery, radiation therapy, chemotherapy, intrapleural therapy, and combined-modality therapies, have had varying impacts on survival. This paper explores current trends in the treatment of malignant pleural mesothelioma.

Antineoplastic Agents↗
PubMed1995

Pharmacokinetics of paclitaxel and carboplatin in combination.

We studied the pharmacokinetics of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin administered in combination to 21 patients with advanced non-small cell lung cancer. Paclitaxel was administered as a 24-hour intravenous infusion at doses of 135 to 200 mg/m2. Carboplatin, dosed to a target area under the concentration-time curve of 5, 7, 9, or 11 mg/mL.min, was administered as a 20-minute infusion immediately following paclitaxel. Neither the paclitaxel concentrations at the end of the infusion nor the terminal elimination of paclitaxel, as assessed by the duration of time that plasma paclitaxel concentrations were 0.05 mumol/L or greater, were different compared with historical data of paclitaxel as a single agent. Thus, we concluded that carboplatin had no perceived effect on the pharmacokinetics of paclitaxel in this schedule. The observed areas under the concentration-time curves for carboplatin were consistently 10% to 15% less than the target values. Although this may indicate a possible interaction between paclitaxel and carboplatin, it also may have been a result of inadequate assessment of glomerular filtration rate, which was used to determine the carboplatin dose.

Adult↗
PubMed1995

Feasibility and pharmacokinetics of paclitaxel, carboplatin, and concurrent radiotherapy for regionally advanced squamous cell carcinoma of the head and neck and for regionally advanced non-small cell lung cancer.

Sequential chemotherapy and radiotherapy offer considerable improvements in the care of patients with locally advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Improved survival for lung cancer and organ preservation in head and neck cancer have occurred with this approach, but local control remains a problem. Concurrent chemotherapy and radiotherapy can potentially improve both local control and control of micrometastases. We previously showed that concurrent carboplatin plus radiotherapy is a useful potential treatment for advanced NSCLC and SCCHN, producing good local control and acceptable toxicity. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has recently demonstrated strong single-agent activity against both NSCLC and SCCHN. Paclitaxel has also shown favorable interactions with radiotherapy and with platinum compounds. We therefore added weekly paclitaxel at 45 mg/m2 given after premedication and before carboplatin (100 mg/m2) weekly during concurrent standard-dose radiotherapy. Twenty patients (seven with SCCHN and 13 with NSCLC) have been treated (38 and 73 weekly doses, respectively). Toxicities have been manageable with delay or dose reduction in five and eight patients, respectively, for SCCHN and NSCLC. Based on these toxicities paclitaxel dose has been reduced to 40 mg/m2/wk. Plasma pharmacokinetics have shown that concurrent carboplatin and radiotherapy do not alter the pharmacokinetic behavior of paclitaxel compared with single-agent data. Concurrent therapy with carboplatin, paclitaxel, and radiotherapy is feasible on this schedule. Further case accrual to assess efficacy is ongoing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Combined modalities in the treatment of head and neck cancers.

The higher the T and N stages at diagnosis of head and neck cancer, the lower the proportion of patients who achieve complete, durable local control and the lower the survival. These cancers and their treatments often produce considerable anatomic distortion, affecting function, nutritional status, and appearance. New treatment approaches for locally and regionally advanced head and neck cancers are thus needed to improve survival, quality of life, or both. Combined-modality approaches show promise. Induction chemotherapy and subsequent radiotherapy produce results equivalent to aggressive surgery but allow for better organ function and speech. Induction chemotherapy and radiotherapy are superior to radiotherapy alone. Concurrent chemotherapy and radiotherapy may produce additive or synergistic interactions but increase toxicities. Some studies suggest that concurrent chemotherapy and radiotherapy significantly improves survival over radiotherapy alone in regionally advanced disease. Drug selection criteria have included enhancement of radiation cytotoxicity, effect on cellular kinetics, and, possibly, single-agent antitumor activity. The platinum compounds are of interest, especially in combination with other chemotherapy agents, like 5-fluorouracil and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). Concurrent carboplatin and radiotherapy produced a 77-week duration of survival in responders in a University of Maryland Cancer Center study. A study of concurrent carboplatin/bleomycin/radiotherapy had to be halted because of severe bleomycin-induced mucositis. The results in this small group suggest that attenuating mucositis would be desirable. In a subsequent trial, paclitaxel, which shows considerable activity against head and neck cancers, was substituted for bleomycin. Data from the seven patients accrued thus far are too immature to define response. The study continues to accrue patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Paclitaxel and carboplatin with and without filgrastim support in patients with metastatic non-small cell lung cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ) and carboplatin have each shown activity against non-small cell lung cancer and they are synergistic in vitro. We thus designed a phase I study to define the maximum tolerated dose and dose-limiting toxicity of the combination with and without filgrastim support. With an initial fixed dose of paclitaxel 135 mg/m2 given as a 24-hour infusion, carboplatin was administered in escalating doses in cohorts of three patients, based on a target area under the concentration-time curve (AUC) of 5, 7, 9, or 11 using Calvert's formula: dose (mg) = target AUC x (glomerular filtration rate + 25). Dose escalations were based on course I toxicities. Filgrastim 5 micrograms/kg was administered with the first cycle only after grade 4 neutropenia occurred in two of three patients at the prior dose level. One hundred five courses of paclitaxel and carboplatin have been administered in 26 patients. Dose-limiting toxicity (grade 4 neutropenia) occurred in two patients at level 2 (cycle I). Filgrastim was instituted thereafter with cycle I for the next four levels. Grade 4 thrombocytopenia was seen at level 4; thus, the carboplatin dose was de-escalated in the next level, but the paclitaxel dose was escalated. The regimen has been well tolerated. One patient had a complete response and 12 had partial responses, for an overall response rate of 50%. There is a suggestion of a dose-response effect with both paclitaxel and carboplatin. The combination of paclitaxel and carboplatin is active in non-small cell lung cancer, and the recommended phase II doses for the combination without filgrastim support are paclitaxel 175 mg/m2 as a 24-hour infusion with the carboplatin dose based on a target AUC of 7. The phase II dose with filgrastim support will be defined as dose escalation of paclitaxel continues.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Etoposide: current status and future perspectives in the management of malignant neoplasms.

Etoposide has demonstrated highly significant clinical activity against a wide variety of neoplasms, including germ-cell malignancies, small-cell lung cancer, non-Hodgkin's lymphomas, leukemias, Kaposi's sarcoma, neuroblastoma, and soft-tissue sarcomas. It is also one of the important agents in the preparatory regimens given prior to bone marrow and peripheral stem-cell rescue. Despite its high degree of efficacy in a number of malignancies, the optimal dose, schedule, and dosing form remain to be defined. It is possible that continuous or prolonged inhibition of the substrate, i. e., topoisomerase II, may be the key factor for the cytotoxic effects of etoposide. Clinical studies have shown the activity of etoposide to be schedule-dependent, with prolonged dosing, best accomplished by the oral dosing form, offering a therapeutic advantage. This benefit awaits validation by prospective randomized studies, some of which are in progress. Recent clinical investigations have focused on the use of etoposide in combination with (a) cytokines to ameliorate myelosuppression, the dose-limiting toxicity of etoposide; (b) agents such as cyclosporin A and verapamil to alter the p-glycoprotein (mdr1) function; and (c) topoisomerase I inhibitors to modulate the substrate upon which it acts. There is continued interest in the development of etoposide to its maximal clinical dimensions and in the examination of alternative biochemical and mechanistic approaches to further our understanding of this highly active agent.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Chemoradiotherapy for the treatment of regionally advanced head and neck cancers.

Despite the use of aggressive surgery and radiotherapy, patients with locoregionally advanced squamous cell carcinoma of the head and neck continue to suffer poor local control and poor survival. Chemotherapy produces excellent regressions of locoregional disease when given as part of initial induction therapy. The use of chemoradiotherapy for regionally advanced disease offers the possibility of organ preservation and retention of organ function for many of these patients. Randomized studies have suggested that chemoradiotherapy also offers better local control and survival than radiotherapy alone. Many chemotherapy regimens used in modern chemoradiotherapy include cisplatin. Because of its ease of outpatient administration, lesser degree of nausea and vomiting, reduced nephrotoxicity, improved nutritional status during therapy, and predictable myelotoxicity, carboplatin has important advantages over cisplatin. Carboplatin possesses well-defined single-agent activity against head and neck cancers, and produces excellent responses in combination with 5-fluorouracil in previously untreated patients. Sequential studies at the University of Maryland Cancer Center showed that weekly carboplatin could be safely and easily combined with standard doses and fractions of radiotherapy. With this regimen, 57% of the patients achieved a complete response and 21% achieved a partial response. Although the addition of bleomycin to this regimen proved somewhat toxic, concurrent carboplatin and radiotherapy allows for the further testing of new agents in developing a combination chemotherapy/concurrent radiotherapy program. Such regimens may improve local control and survival, and may be developed further for organ preservation studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Combined chemotherapy and radiation in locally advanced non-small cell lung cancer.

The majority of patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC) treated with conventional radiation therapy develop distant metastases and succumb to the disease. Thus, NSCLC should be viewed as a systemic disease, and attempts to control micrometastatic disease with chemotherapy should have a greater impact on survival. This does not eliminate the role of radiation therapy, as locoregional control is equally important. Combined chemoradiotherapy has become the major area of clinical research to improve long-term outcomes in patients with locally advanced NSCLC. The optimal chemoradiotherapy sequence is yet to be determined. Several randomized studies have demonstrated that sequential chemotherapy followed by definitive thoracic irradiation is superior to the same radiation therapy alone. The overall impact has been on both survival and incidence of distant metastasis. A number of pilot studies (phase II) have tested concurrent chemoradiotherapy in patients with locally advanced NSCLC. At the University of Maryland Cancer Center, we are evaluating the efficacy of thoracic radiation (60 Gy) with concurrent weekly carboplatin, which has known activity in NSCLC and also has radiosensitizing effects. Preliminary results show that the combination is feasible and well tolerated; median survival rates compare favorably to those seen in the combined-modality arms of the randomized, sequential studies. Definitive conclusions based on the results of the reported studies are not possible, yet there seems to be a potential benefit to adding chemotherapy to radiation therapy. These trials need to be confirmed before they can be used to define a "standard of care" for patients with locally advanced, unresectable NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Immunomodulation of interleukin-2 by cyclophosphamide: a phase IB trial.

The objective of this phase IB trial was to determine if cyclophosphamide (CY) could enhance the immune effects of interleukin-2 (IL-2), and if it could, was there an optimal immunomodulatory dosage. IL-2 alone at 30 million IU/m2 thrice weekly for 6 weeks or in combination with varying dosages of CY (300, 600, and 1,200 mg/m2) administered 3 days before IL-2 and repeated 3 weeks later was given to consecutive cohorts of patients (at least five per group) with advanced malignancies of varying types. To gauge the immune effects of the treatment, the variation in the amount of lymphokine-activated killer (LAK) cells generated in the peripheral blood mononuclear cells of patients and in a control group of normal volunteers was measured weekly over 7 consecutive weeks. Other immune parameters [natural killer cells (NK), peripheral blood eosinophils and lymphocytes, cell surface markers, soluble IL-2 receptor, and IL-2 antibodies] were also closely followed to study if they correlated with the degree of LAK activity. The group of patients that received low-dosage CY (300 mg/m2) and IL-2 produced the highest and most sustained levels of LAK and NK activity (p < 0.05) when compared with the cohorts receiving IL-2 alone or to those receiving the higher dosages of CY. No other immune parameter showed a significant difference between the groups. Although low-dosage CY does increase the LAK activity seen with IL-2, only randomized clinical trials can determine if this enhancement will improve tumor responses.

Adult↗
PubMed1993

Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B.

PURPOSE: The impact of the side effects of megestrol acetate on the quality of life of noncachectic women with advanced breast cancer was studied in a dose-response clinical trial of the Cancer and Leukemia Group B (CALGB 8741). Side effects of appetite increase and weight gain at higher doses were predicted to have a negative effect on quality of life. PATIENTS AND METHODS: Stage IV breast cancer patients were randomized to receive either 160, 800, or 1,600 mg/d of megestrol acetate. Quality of life was assessed in 131 patients at trial entry and at 1 and 3 months while on treatment, by telephone interview, using the following measures: the Functional Living Index-Cancer (FLIC), Rand Functional Limitations Scale, Rand Mental Health Inventory (MHI), the Body Image Subscale, and linear analog scales of drug side effects. RESULTS: At 3 months, women treated with 160 mg/d reported less severe side effects (P < .0005), better physical functioning (FLS, P < .0005), less psychologic distress (MHI, P = .008), and an improvement in overall quality of life (FLIC, P = .003) from the time of study entry as compared with those treated with 1,600 mg/d. Patients who received the 800-mg/d dose fell between the low- and high-dose arms in reported intensity of drug side effects, but responded similarly to those in the 160-mg/d group in terms of physical functioning, psychologic distress, and overall quality of life. CONCLUSION: Unless additional follow-up data demonstrate a survival advantage at higher doses, the 160-mg/d dose is optimal, achieving maximal treatment effect with the fewest side effects and better quality of life.

Appetite↗
PubMed1993

Pregnancy outcome in patients treated for Hodgkin's disease.

PURPOSE: This study attempted to determine the outcome of pregnancies in patients (or their partners) who were successfully treated for Hodgkin's disease and to assess the effect of treatment on the children of the treated parents. MATERIALS AND METHODS: A questionnaire was distributed to and personal interviews were conducted with patients who were of reproductive age at the time of treatment with consecutive protocols of radiotherapy, chemotherapy, or both. Those premenopausal patients (or the sexual partners of patients) who attempted to conceive after successful treatment constituted the study population. Fertility assessment was based only on those patients identified as desiring children. RESULTS: Among 391 adult patients, 221 patients (104 females and 117 males) of reproductive age were interviewed. Before treatment, 63 of the 221 patients had 135 pregnancies, which resulted in 118 children, 11 spontaneous abortions, five elective abortions, and one stillborn. After treatment, 94 patients (43 females and 51 males) actively attempted conception; 35 females and 25 partners of male patients had 84 pregnancies, which resulted in 68 living children. Among the 84 pregnancies, there were one premature birth at 29 weeks, three spontaneous abortions, 11 elective abortions, and two stillborn: one at 32 weeks and one set of twins. The children have been observed for a median of 11 years (minimum follow up > 4.5 years). Of those patients who desired children, 35 of 43 females became pregnant, whereas only 25 of the 51 partners of male patients became pregnant. At least five male patients with low sperm counts apparently fathered children. CONCLUSIONS: This study demonstrates that both men and women have the potential for fertility after treatment regardless of treatment modality. The partners of male patients who were treated with combined modality treatment had a lower frequency of pregnancy than did the female patients who attempted conception and their frequency of pregnancy was also lower than the general population. There was no apparent increase in complications of pregnancy, spontaneous abortions, or congenital abnormalities after treatment compared with pregnancies in this patient group before treatment or with pregnancies in the general population.

Adolescent↗
PubMed1993

Randomized phase II trial of cisplatin with mitomycin or doxorubicin for malignant mesothelioma by the Cancer and Leukemia Group B.

PURPOSE: The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II multicenter trial to evaluate the activity of two cisplatin-containing regimens (cisplatin and mitomycin [CM], or cisplatin and doxorubicin [CD]) in patients with malignant pleural or peritoneal mesothelioma (protocol CALGB 8435). PATIENTS AND METHODS: Seventy-nine patients were entered between June 1984 and October 1986. Eligibility included a performance status of 0 to 2 by CALGB criteria, and no prior chemotherapy. Central pathology review was performed. Randomization was stratified according to the cell type (epithelial v mixed or sarcomatous) and the presence of measurable versus assessable disease. Of the 79 patients entered, 70 were included in this analysis (35 on CM and 35 on CD), including 48 with epithelial cell type and 22 with mixed or sarcomatous cell types. Sixty-six patients had pleural mesothelioma and four had peritoneal mesothelioma. There were 34 cases with measurable disease and 36 with assessable disease. RESULTS: The overall response rate was 26% for CM (two complete responses [CRs], three partial responses [PRs], and four regressions) and 14% for CD (four PRs and one regression). Median time to treatment failure was 3.6 months for CM and 4.8 months for CD, and median survival duration from study entry was 7.7 and 8.8 months, respectively, with no significant differences between treatments. Good performance status (0 or 1) was associated with significantly longer survival duration (P = .013). Both regimens were well tolerated and there were no treatment-related deaths due to toxicity. CONCLUSION: Moderate antitumor activity has been observed with both regimens. In this randomized phase II trial, the overall response rates, time to treatment failure, and overall survival appear to be similar for the two regimens tested.

Antineoplastic Combined Chemotherapy Protocols↗