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Biomedical subjects

H B Muss

Publications and source records attributed to H B Muss.

At least 163 records · Page 9Linked to original sources

PALA (NSC-224131) in advanced carcinoma of the cervix. A phase II study of the Gynecologic Oncology Group.

Thirty-six patients with advanced carcinoma of the cervix received PALA at a dosage of 5 gm/m2 every three weeks. Thirty-three patients had received prior irradiation therapy and chemotherapy. No complete or partial responses were seen. The major toxicity was dermatologic and occurred in 16/36 (44%) of patients. Three patients experienced dose limiting disorientation or confusion. PALA was not associated with any antitumor activity in patients with advanced carcinoma of the cervix who had received prior chemotherapy. The results of this study indicate that PALA has no substantial activity in patients with advanced squamous carcinoma of the cervix who have previously received chemotherapy.

Adult↗

VP-16-213 in combination chemotherapy with chest irradiation for small-cell lung cancer: a randomized trial of the Piedmont Oncology Association.

The role of etoposide epipodophyllotoxin (VP-16-213) in a combined modality treatment program incorporating local chest irradiation and combination chemotherapy with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine has been evaluated in a randomized trial of 165 patients with small-cell lung cancer. The overall response rate (complete response [CR] plus partial response [PR]) was significantly greater in the VP-16-213 arm (85% v 64%, P = .005) primarily as a consequence of improved response in patients with extensive disease (85% v 38%, P = .002 and 30% v 8% for CR only, P = .045). No differences in the response rates were observed in limited disease. The duration of response (months) was greater in the VP-16-213 arm (8.6 v 7.0 overall and 14.4 v 11.5 for CR) but not significantly so. Median survival times (months) were consistently greater in the group receiving VP-16-213 when analyzed according to extent of disease and response (10.6 v 9.5 overall; 15.0 v 13.6 for limited disease; 9.0 v 6.7 for extensive disease; 18.5 v 16.2 for CR overall; and 18.6 v 16.1 for CR in limited disease); the results were not statistically significant. The median survival of extensive disease patients attaining a CR was 15.3 months (range 3.2 to 34.3 + months) in the VP-16-213 arm and 7.4+ and 8.1+ months for the two patients with CR in the other group. Anemia and leukopenia occurred to a greater degree in the four-drug regimen, but no unusual or significant compounding toxicity (ie, neurotoxicity) was observed otherwise. Further investigation of this agent in combination chemotherapy programs for small-cell lung cancer appears to be warranted.

Adult↗

A phase II study of recombinant alpha interferon in patients with recurrent or metastatic breast cancer.

Thirty-three patients with advanced breast cancer were treated with a recombinant alpha interferon (rIFN-alpha 2). All patients were ambulatory (performance status greater than or equal to 50 Karnofsky scale) and almost all had received previous chemotherapy. Large intravenous dosages of 30 to 50 X 10(6) IU/m2 were given for five consecutive days every two to three weeks to 22 patients and smaller subcutaneous dosage of 2 X 10(6) IU/m2 three times a week to 11 patients. No complete or partial responses were seen. Two patients had stable disease and the remainder progressed. Flu-like syndromes were seen in all patients. Nausea, vomiting, and anorexia were frequent. Hypotension and confusion were noted in six and five patients, respectively. Life-threatening leukopenia was noted in two patients receiving intravenous dosage and thrombocytopenia was noted in one; no sepsis or bleeding complications were noted. In this study, a highly purified and biologically active rIFN-alpha 2 was not associated with activity in previously treated women with metastatic breast cancer.

Adult↗

Thyroid cancer.

Thyroid cancers are especially common in patients who have received irradiation to the head and neck region for benign diseases. Well-differentiated papillary and/or follicular carcinomas are the most common types of thyroid cancer. They grow slowly and have a very good prognosis when managed with an appropriate combination of surgical and medical therapy. Other types of thyroid cancer often require more intensive therapy and follow-up. It is especially important to evaluate relatives of patients with medullary thyroid cancer.

Adenocarcinoma↗

Chemotherapy of advanced squamous carcinoma of the cervix: a phase I-II study of high-dose cisplatin and cyclophosphamide. A pilot study of the Gynecologic Oncology Group.

Sixteen patients with recurrent squamous cell carcinoma of the cervix were treated with a combination of cyclophosphamide and cisplatin to determine a tolerable dose schedule, major adverse effects, and a general estimate of response rate and duration. Toxicity was substantial with a dose of cyclophosphamide 1000 mg/m2 and cisplatin 100 mg/m2 given intravenously every 3 weeks. Renal, hematologic, and gastrointestinal toxicities were severe. Of the 12 patients with measurable disease, there were two complete responses and three partial responses for a response rate of 42%. The median duration of response was 24 weeks. Six patients remained stable during therapy and one patient had progression of disease. Use of cyclophosphamide and cisplatin in combination chemotherapy for recurrent carcinoma of the cervix was tolerable but associated with substantial toxicity. The responses seen in this study are encouraging and warrant further comparative trials with this combination of drugs.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment of poor risk acute leukemia with sequential high-dose ARA-C and asparaginase.

Resistance of leukemia cells to cytosine arabinoside (ARA-C) may be due to any one or combination of biochemical processes, which in certain instances may be substantially reversed by an appropriate increase in ARA-C dosage. Based on these and other laboratory observations indicating pharmacologic synergy between sequential high-dose ARA-C and asparaginase (HiDAC----ASNase), a therapeutic program was developed for the treatment of patients with acute nonlymphocytic leukemia (ANLL) refractory to conventional doses of ARA-C, as well as patients with high risk ANLL and advanced acute lymphocytic leukemia (ALL). Treatment consisted of 3-hr intravenous infusions of 3 g/sq m of ARA-C given at 12-hr intervals for 4 doses, followed by 6,000 IU/sq m ASNase given i.m. at hour 42. The same schedule was repeated on day 8. In 32 induction attempts, only 4 patients proved to be truly refractory, i.e., failed to achieve substantial leukemia cell cytoreduction. Complete remissions were achieved with HiDAC---- ASNase in 9 of 13 patients with refractory ANLL, 6 of 9 patients with antecedent hematologic disorders, and 3 of 10 patients with advanced ALL. These include 9 of 14 patients who had either failed induction or who had relapsed on active ARA-C therapy and 6 of 8 patients who had had no prior exposure to ARA-C. The median duration of unmaintained remission in ANLL was 5 mo. In a patient with central nervous system (CNS) leukemia, there was clearance of cerebral spinal fluid (CSF) blasts without intrathecal therapy, suggesting a role for HiDAC in CNS prophylaxis. In general, toxicity was tolerable and reversible. These data suggest that HiDAC----ASNase is an exceptionally effective and well tolerated regimen in leukemic patients with antecedent hematologic disorders and in those refractory to conventional doses of ARA-C.

Acute Disease↗

Thymoma.

Thymomas, with their diverse signs, symptoms and relationships to other systemic diseases, are not infrequently encountered. Histologic classification is now standardized. Thymoma is associated with other disorders, such as myasthenia gravis and pure red cell aplasia. Proper staging, careful histologic evaluation and appropriately selected therapy are necessary to ensure long-term survival.

Anemia, Aplastic↗

Informed consent: patient information forms in chemotherapy trials.

Documentation of informed consent by patients entering clinical trials is an ethical and legal necessity. Federal regulations and judicial opinions have led to increasingly lengthy, detailed "consent" forms, yet published studies demonstrate that patients remain confused about the nature and anticipated consequences of study entry. It has been suggested that more detail may even alarm or further confuse patients. Seventy-five women undergoing chemotherapy for advanced breast cancer participated in this study which assessed patient preference for long-, medium-, or short-form length, and whether form length preference correlated with patient characteristics or indicators of patient autonomy in decision-making or physician dependency. Patient preferences for information were not predicted by the patient autonomy or physician dependency scores or by age, marital status, or level of education. The majority of patients expressed a preference for more detailed information about their treatment, yet a majority of patients given detailed forms answered questions basic to the study design incorrectly, irrespective of educational level. The increased detail included in the long forms was not reported to increase stress compared to the short forms. Patient information forms are a principal tool for informing patients for consent but if they are to perform their desired function they must be designed more carefully and evaluated more thoroughly than in the past.

Age Factors↗

CCNU in combination chemotherapy for advanced histologically unfavorable non-Hodgkin's lymphoma.

During a 3-year period 39 evaluable patients with stage III and IV non-Hodgkin's lymphomas and unfavorable histologies were treated with a unique chemotherapeutic regimen based on a modified CHOP combination to which was added the nitrosourea, CCNU. Complete response was observed in six of 15 (40%) patients with diffuse poorly differentiated lymphocytic lymphoma (DPDL), four of 11 (36%) with diffuse mixed histiocytic lymphocytic (DML), and seven of 13 (54%) with diffuse histiocytic lymphoma (DHL). Of the 17 patients who achieved complete response, nine (53%) have remained continuously disease-free for greater than 2.5 years (2.7-4.1 years) from the onset of therapy: four of six with DPDL, two of four with DML, and three of seven with DHL. Median survival was 18.9 months for all patients, 18.9 months for those with DPDL, 17.4 months for those with DML, and 9.7 months for those with DHL. The median survival has not been reached for patients who attained a complete response, and will exceed 3.3 years. Central nervous system relapse was observed in three patients. In general, toxicity was moderate and consisted primarily of leukopenia, nausea, vomiting, and neurotoxicity. There were no drug-related deaths. The addition of CCNU to a modified CHOP combination resulted in an effective, generally well-tolerated out-patient regimen. However, it did not appear to decrease the rate of CNS relapse or improve current treatment results observed with other adriamycin-containing regimens for similar patients.

Adolescent↗

Vincristine, doxorubicin and mitomycin (VAM) in patients with advanced breast cancer previously treated with cyclophosphamide, methotrexate and fluorouracil (CMF). A clinical trial of the Piedmont Oncology Association (POA).

Thirty-six evaluable patients with advanced breast cancer who had failed prior CMF therapy [15 (42%) as adjuvant treatment and 21 (58%) for advanced disease] were treated with a combination of vincristine, doxorubicin, and mitomycin (VAM). There was one CR and 10 PR, giving a response rate of 31% (P, 95% confidence interval, 15%-47%). Response was not significantly related to age, performance status, disease-free interval, dominant site of disease, number of sites of disease, or estrogen receptor status. The median duration of response was 5 months for patients attaining CR or PR and 4.6 months for patients with stable disease. The median survival for patients with CR or PR of 7.9 months was not better than for those with stable disease (8.0 months), but both groups had significantly longer survival than those with initial progression. Patients who received VAM after failing adjuvant CMF had a 53% response rate (8 of 15), as against a 14% response rate (3 of 21) in those failing CMF for advanced disease (P less than 0.05). In spite of this difference, the survival distributions for these two groups were not significantly different. Myelosuppression was moderate and no cardiac toxicity was seen. The addition of mitomycin to vincristine and doxorubicin in previously treated patients does not appear to improve the results obtained with vincristine and doxorubicin alone.

Adult↗

Lack of potentiation of vincristine-induced neurotoxicity by VP-16-213.

Due to a recent alarming report suggesting that the severe neurotoxicity observed following treatment with a multiagent chemotherapy regimen might be due to the interaction of vincristine and VP-16-213, the neurologic toxicity data from a randomized trial conducted by the Bowman Gray School of Medicine and the Piedmont Oncology Association in small cell carcinoma of the lung have been analyzed. Of 102 patients evaluable for toxicity, 50 were treated with a combination of cyclophosphamide, adriamycin, and vincristine (CAV) and 52 received this regimen plus VP-16-213. Vincristine dosage was the same in both arms of the study. When analyzed by severity, neurologic complications were similar in both treatment groups: Grade 1-2 neurotoxicity occurred in 55% of patients on both arms and grade 3-4 neurotoxicity was observed in six (12%) patients on the CAV arm and four (8%) on the CAV-VP-16-213 arm. Addition of VP-16-213 to vincristine did not potentiate vincristine-induced neurotoxicity when administered in this dose-schedule relationship.

Adult↗

Multiple primary bronchogenic carcinomas of the lung.

The problem of multiple primary bronchogenic carcinomas in a single patient is not well known to radiologists. Six patients who exemplified the clinical, radiographic, and pathologic difficulties in diagnosis are reported. The most frequent pathologic associations are squamous carcinoma and squamous carcinoma, squamous carcinoma and small-cell carcinoma, and squamous carcinoma and adenocarcinoma. The previously undescribed association of small-cell carcinoma and bronchioloalveolar cell carcinoma was present in one of six patients. While many patients have a synchronous presentation, the tumors are metachronous in 66%. Since the incidence of second primary carcinoma increases with time, close long-term monitoring is recommended.

Adult↗

Vincristine by continuous infusion in refractory breast cancer: a phase II study.

Eighteen patients with advanced refractory breast carcinoma were treated with vincristine (VCR), 0.5 mg I.V. bolus followed by continuous I.V. infusions of 0.25 mg/m2/day for 5 days every 3 weeks. The daily dose of VCR was infused in 1000 ml D5W to which was added hydrocortisone 50 mg and heparin 3000 U. Patients received from one to six courses (mean 2.3 courses). No objective responses were observed. Stable disease was noted in five patients who had skeletal metastases only. Disease progression occurred in the remaining 13 patients, 10 of whom had received prior VCR by bolus injection. The principal toxicity consisted of constipation without ileus and hyporeflexia-paresthesias. Vincristine, administered by continuous I.V. infusion according to this dose and schedule does not appear to be effective in the treatment of patients with advanced refractory breast cancer.

Breast Neoplasms↗

Treatment of advanced ovarian malignancy with chemoimmunotherapy using autologous tumor and Corynebacterium parvum.

Fourteen patients with advanced ovarian epithelial carcinoma were treated with a combination of chemotherapy and immunotherapy. The chemotherapy consisted of either melphalan or a combination of adriamycin, cytoxan, and cisplatin. The immunotherapy consisted of the injection of autologous radiation-attenuated tumor and Corynebacterium parvum. No significant toxicity occurred as a result of the immunotherapy, and there was no evidence of tumor growth at the sites of injection. The autologous tumor skin test showed prognostic value. Skin testing with C parvum was of less prognostic value than tumor. All other studies of immunologic status, including T- and B-cell enumeration and blastogenic responsiveness of the patients' lymphocytes to autologous tumor and mitogens, were of no prognostic value.

Adenocarcinoma↗

Vincristine, doxorubicin, and cyclophosphamide versus low-dose intravenous cyclophosphamide, methotrexate, and 5-fluorouracil in advanced breast cancer: a randomized trial of the Piedmont Oncology Association.

Eighty-one evaluable patients with recurrent or metastatic breast cancer were randomized to receive either vincristine 1 mg/m2, doxorubicin 40 mg/m2 on day one and cyclophosphamide 200 mg/m2 orally days 3-6 (VAC); or cyclophosphamide 350 mg/m2, methotrexate 20 mg/m2, and 5-fluorouracil 350 mg/m2 (CMF) intravenously, all on day 1. Courses of each of the above regimens were repeated every three weeks. Twenty-one of 45 patients (47%) on VAC and seven of 44 patients (16%) on CMF had complete or partial response (P less than 0.05). The duration of response was six months for CMF and nine months for VAC. Hematologic toxicity was minimal for both groups but three patients receiving VAC developed cardiac toxicity. Overall survival projections at this time indicate no differences between the VAC or CMF treated patients.

Antineoplastic Agents↗

Nonseminomatous germ cell cancer of the testis. Reducing treatment-related morbidity in patients with disseminated disease.

Fourteen previously untreated patients with metastatic nonseminomatous germ cell cancer of the testis (NSGC) were treated with a modified VAB-4 regimen which was designed to reduce treatment-related morbidity. Nine of 10 patients with minimal disease and the only patient with advanced pulmonary disease achieved a complete response (CR) with chemotherapy alone. Two of three partial responders with advanced abdominal disease were converted to CR status with radiotherapy and/or surgery. None of the 12 CRs have relapsed (median duration of follow-up, 28+ months). We observed no granulocytopenic fever or permanent renal insufficiency. These results indicate that NSGC patients with a low tumor burden can be spared substantial toxicity without adversely affecting complete response rates.

Antineoplastic Agents↗

Nonseminomatous germ-cell cancer of the testis.

Fourteen previously untreated patients with metastatic nonseminomatous germ-cell cancer of the testis (NSGC) were treated with a modified VAB-4 regimens that was designed to reduce treatment-related morbidity. Nine of ten patients with minimal disease and the only patient with advanced pulmonary disease achieved a complete response (CR) with chemotherapy alone. Two of three partial responders with advanced abdominal disease were converted to CR status with radiotherapy and/or surgery. None of the 12 CRs has had a relapse (median duration of follow-up, 28+ months). We observed no granulocytopenic fever or permanent renal insufficiency. These results indicate that NSGC patients with a low tumor burden can be spared substantial toxicity without the complete response rates being adversely affected.

Antineoplastic Agents↗

Combination chemotherapy-radiotherapy with and without the methanol-extraction residue of Bacillus Calmette-Guerin (MER) in small cell carcinoma of the lung: a prospective randomized trial of the Piedmont Oncology Association.

The effect of addition of the nonspecific immunostimulant, MER, to combined treatment with chemotherapy and radiotherapy in small cell carcinoma of the lung was evaluated in a prospective randomized trial involving 102 evaluable patients. Chemotherapy consisted of cyclophosphamide, Adriamycin, vincristine, methotrexate, and CCNU; and radiotherapy was administered to the primary lesion, mediastinum, supraclavicular areas, and whole brain. Of 47 patients administered MER 400 mcg intradermally every six weeks, 12 (26%) attained complete remission with a median survival of 22.9 months. Complete remission was observed in 17 (31%) of 55 patients who received no MER with a median survival of 20.0 months (P greater than 0.05). Survival greater than or equal to 2 years has been observed in five patients who received MER and two patients who did not receive MER. The response rate and duration, survival, and toxicity of the two treatment arms were similar with the exception of cutaneous and occasional systemic reaction to MER. MER as used in this study has not influenced the overall results of a combined modality treatment program for patients with small cell carcinoma of the lung.

Adult↗