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Biomedical subjects

D A Amato

Publications and source records attributed to D A Amato.

27 records · Page 2Linked to original sources

Early peritoneal mesothelioma: a treatable malignancy.

37 patients with malignant peritoneal mesothelioma were studied to assess the efficacy of combined therapy. 14 patients presented after 1982. Of 6 patients treated intensively, all remain alive with no evidence of disease by computed tomographic scan at 9-36 months. Of 8 patients treated palliatively, 5 are dead. (5 had stable disease, 1 has progressed despite all treatment, and 2 were not treated.) Survival of the intensively treated group is significantly better than that of other stage I patients in this series. Patients under 40 had a significantly better survival rate than older patients.

Adolescent↗

Patterns of relapse in locally advanced head and neck cancer patients who achieved complete remission after combined modality therapy.

Relapse patterns in patients with locally advanced head and neck cancer who achieved complete remission were evaluated. After combined modality therapy with induction chemotherapy followed by surgery and/or radiotherapy, 71 of 103 patients were clinically free of disease. The 5-year recurrence rate was estimated at 51%, with a 39% local and 26% distant failure rate by 5 years. The factors significantly affecting the relapse patterns were: the site of the primary tumor (those with oral cavity lesions were more likely to fail locally, whereas hypopharynx patients had a higher risk of distant metastases); the type of definitive local treatment (those patients who received surgery and radiotherapy were at lower risk of pure local failure); TN Stage (patients with T4N3 or T3N3 tumor were at higher risk of both local and distant failure); and time to response and presence of oropharyngeal lesions (patients who had a longer period from diagnosis to final complete response [CR] and patients with oropharyngeal primaries were at higher risk for simultaneous local and distant failure). Type of chemotherapy, patient age, tumor differentiation, and response to induction chemotherapy did not significantly influence the patterns of relapse. A combined modality approach with induction chemotherapy, surgery, and/or radiotherapy does not seem to reduce the incidence of distant metastases significantly.

Adult↗

Evaluation of bleomycin, chlorozotocin, MGBG, and bruceantin in patients with advanced soft tissue sarcoma, bone sarcoma, or mesothelioma.

Patients with objectively measurable soft tissue sarcoma, bone sarcoma, or mesothelioma who had failed at least one prior chemotherapy regimen received either bleomycin (20 U/M2 i.v. day 1 each week), chlorozotocin (150 mg/M2 i.v. q6 weeks), MGBG (500 mg/M2 i.v. each week, escalated in 50 mg/M2 weekly increments to a maximum dose of 700 mg/M2), or bruceantin (5.5 mg/M2 days 1, 8, 15, and 22, with cycles repeated every 6 weeks). One hundred eighty patients were evaluable: 53 on bleomycin, 51 on chlorozotocin, 38 on MGBG, and 38 on bruceantin. Two partial responses resulted from bleomycin, and one each from chlorozotocin and MGBG. Both responders on bleomycin had mesothelioma. Seventy-four percent of the patients were of ECOG performance status 0 or 1, and over half on each arm had moderate or worse toxicity. At these doses and schedules, none of the four drugs tested was active against previously treated sarcomas. Bleomycin, however, should be considered for further evaluation in mesothelioma patients.

Adolescent↗

Split-course radiotherapy of carcinoma of the urinary bladder stages C and D1. A Radiation Therapy Oncology Group Study.

One hundred forty-eight patients with advanced carcinoma of the urinary bladder Stages C or D1 were randomized between continuous-course radiotherapy (6,000 cGy in 30 fractions of 200 cGy each, over 6 weeks) and split-course radiotherapy (2,750 cGy in 10 fractions of 275 cGy each, over 2 weeks; a rest period of 3 weeks; 2,750 cGy in 2 weeks); 139 are analyzed in this report. Ninety-four percent of the patients have been followed at least 5 years or until death. The patients ranged in age from 45 to 80 with a median of 69. Seventy-six percent of the patients were males and 58% had Stage C disease. In patients with information on the size of the tumor, in 66% the lesion measured 5 cm or larger; 26% had a diameter of 8 cm or larger. In general, the treatment groups were well balanced with respect to patient characteristics. Both treatment groups tolerated therapy well. Eighty-seven percent of the patients completed therapy, 66% as planned. Fifty-four percent experienced at least one severe reaction, with the most common types being diarrhea (28%), frequency of urination (24%), soreness or burning on urination (25%), and urgency of urination (19%). Late effects of therapy were minimal. Median survival times were 11.5 months and 9.4 months for continuous-course and split-course, respectively. The treatment differences were not significant (p = 0.88; Mantel-Haenszel stratified by stage and sex). Forty percent of the patients became free of all clinically detectable disease following radiotherapy either alone or in combination with additional surgery (40% for continuous-course, 4% cleared by surgery, and 39% for split-course, 3% cleared by surgery). When the tumor measured less than 5 cm, the clearance rate was 61% (20/33) vs. 33% (13/39) for 5-7.9 cm, and 24% (6/25) for 8 cm or larger (p less than 0.01; chi2 test for linear trend). For those who became disease free, median time disease free within the irradiated volume was 72 months for continuous-course and is currently undefined for split-course; median time disease free was 28 months and undefined, respectively. There were no significant treatment differences in tumor control for any of these endpoints. The ultimate long-term tumor control in the pelvis was 28% (19/68) for continuous- and 25% (18/71) for split-course therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Randomized trial of chlorozotocin, neocarzinostatin, or methyl-CCNU in patients with malignant melanoma.

One hundred twenty-two patients with disseminated malignant melanoma were randomized using an unbalanced randomization to receive chlorozotocin, neocarzinostatin, or MeCCNU. Of the 114 evaluable patients, 46 received chlorozotocin, 47 received neocarzinostatin, and 21 received MeCCNU. The response rates to these three drugs were 9%, 4%, and 14% respectively. Median survival times were 4.2, 3.4, and 5.8 months respectively. Toxicity was acceptable with all three agents. Chlorozotocin and neocarzinostatin do not appear to offer any improved response rates over MeCCNU for patients with disseminated malignant melanoma.

Adult↗

Effect of BCG immunotherapy on N-nitroso-N-methylurea-induced carcinogenesis of guinea pig colon.

A total of 480 guinea pigs each received twice weekly intrarectal instillations of 1 mg N-nitroso-N-methylurea (NMU) during 14-35 weeks (total dose NMU, 28-70 mg) to induce colon neoplasms. At 24, 28, or 35 weeks after the start of NMU instillation, the distal colon was exposed by a ventral laparotomy and suspected neoplastic lesions were treated by one of four methods: A, intratumoral instillation of an emulsion of killed BCG cell walls attached to oil droplets; B, intratumoral instillation of a control emulsion of killed BCG cell walls in an aqueous phase rather than lipid phase; C, surgical excision of the colon lesion with formation of a ventral diverting colostomy; or D, sham operation (no treatment). All guinea pigs were allowed to recover from surgery and were then observed for a period of 1 year for the study of the effects of these treatments on NMU-induced colon neoplasms. Colon neoplasms were produced in 76% of all sham-operated control guinea pigs, and the frequency of such neoplasms was dependent on the total dose of NMU. Most neoplasms were adenocarcinomas with invasion of the bowel wall but only approximately 5% of them metastasized. Treatment with BCG failed to alter the course of NMU-induced colon carcinogenesis, as determined by the frequency of colon neoplasia, the number, the gross, or microscopic characteristics of colon neoplasms, or the rate of survival.

Animals↗

Survival of patients with localized high-grade soft tissue sarcoma with multimodality therapy. A matched control study.

Ten of 16 consecutive patients (63%) with Stages III-IVA soft tissue sarcoma presenting between 1975 and 1978 and treated with surgery, radiotherapy and adjuvant chemotherapy have remained disease-free with a median follow-up of three years (range, 28-68 months). Survival at three years was 86%. However, in the American Joint Committee (AJC) soft tissue sarcoma staging system published in 1977, Grade 3 soft tissue sarcomas were associated with a three-year survival of 35% and almost 90% of the patients destined to fail did so within three years of diagnosis (8). To determine if the observed improvement in survival resulted merely from lesions with favorable prognostic determinants at diagnosis, study patients were matched for stage, histologic type and location of the primary lesion with controls generated from these 1215 carefully reviewed sarcoma patients collected from the data base of the Task Force on Soft Tissue Sarcomas of the AJC. Only control cases whose histology had been reviewed and who had been treated with surgery (with or without radiotherapy) were included in the analysis. Cases survived significantly longer than controls at three years (p less than 0.001) and, in fact, disease-free survival of cases (63%) was superior to overall survival of controls (27%) (p less than 0.01). Our data support the conclusion that patients with high-grade soft tissue sarcoma treated by an experienced multimodality team have a three-year disease-free survival of approximately 63%. The impact of each component of multimodality therapy cannot be determined, and improved survival may result, in addition, from improved diagnostic and staging techniques currently available.

Adult↗

Split-course versus continuous pelvis irradiation in carcinoma of the uterine cervix: a prospective randomized clinical trial of the Radiation Therapy Oncology Group.

In August 1980, the Radiation Therapy Oncology Group (RTOG) completed a prospective randomized clinical trial for the comparison of a split-course versus a standard continuous course of pelvic irradiation for carcinoma of the uterine cervix Stages II-B, III-A, III-B, and IV-A. The split-course consisted of 10 fractions of 250 rad each, 5 times a week, up to 2500 rad followed by a rest period of approximately 2 weeks and then another 2500 rad was given (250 X 10). The continuous course consisted of 30 fractions of 170 rad each, 5 times per week, for a total of 5100 rad. In both groups the external pelvis irradiation was followed by intracavitary brachytherapy in the uterus and vagina, with tandem-colpostat or tandem only, for a dose of 3000 rad at point A for the former, or at 2 cm from the center of the linear source for the latter. In cases where brachytherapy was not possible, a boost of external irradiation with reduced field, with a dose of 1600 rad (200 X 8) was advised. Three hundred and one patients were registered, of which 287 are currently evaluable. No differences between the treatments were detected for the following study end-points: treatment tolerance in terms of acute normal tissue reactions and completion of therapy, tumor control in the pelvis, severe late normal tissue reactions, and survival. In the entire study population the estimated tumor control in the pelvis at two years after initiation of therapy was: 81% for Stage II-B, 67% for III-A, 53% for Stage III-B, and 32% for Stage IV-A. The estimated two-year survival was: 70% for Stage II-B, 58% for III-A, 46% for III-B, and 23% for IV-A.

Adult↗

Specific release of proteoglycans from human natural killer cells during target lysis.

Natural killer (NK) activity is mediated by a small population of peripheral blood cells that exhibit the homogeneous morphology of large granular lymphocytes (LGL). In recent studies, human NK cell clones have been shown to contain a 200,000-Mr (relative molecular mass) protease-resistant chondroitin sulphate A proteoglycan, which has been localized to the secretory granule by X-ray dispersive analysis and by its resistance to cleavage by extracellular addition of chondroitinase AC or ABC (ref. 7). In the present study, we have used six different human NK cell clones to demonstrate that release of 35S-proteoglycan correlates closely with cytolytic activity against various NK cell targets. When NK activity is blocked by monoclonal antibodies at either the effector cell level (LFA-1) or at the target cell level (TNKTAR), there is a concomitant decrease in exocytosis of proteoglycan. Monoclonal antibodies directed against recognition structures, for example anti-NKTa and anti-T3 (ref. 10), function as soluble stimuli, capable of initiating the release of 35S-proteoglycan. Taken together, these results provide strong evidence for the stimulus-specific release of chondroitin sulphate A proteoglycans from NK cells when the cytolytic process is activated.

Antibodies, Monoclonal↗