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Biomedical subjects

L H Einhorn

Publications and source records attributed to L H Einhorn.

At least 19 recordsLinked to original sources

No evidence of acute cardiovascular complications of chemotherapy for testicular cancer: an analysis of the Testicular Cancer Intergroup Study.

PURPOSE: The purpose of this study is to evaluate the risk of acute vascular events in patients receiving cisplatin-based chemotherapy for testicular cancer. PATIENTS AND METHODS: A questionnaire assessing cardiovascular toxicity was distributed to all participants in the Testicular Cancer Intergroup study and details of toxicity from the chemotherapy flow sheets were reviewed. Patients with pathologic stage I testicular cancer were registered on to the study and observed after retroperitoneal lymphadenectomy. Patients with pathologic stage II disease were randomized to receive two postoperative courses of adjuvant cisplatin-based chemotherapy or observation. Any patient who had disease recurrence after observation or adjuvant therapy was given four cycles of cisplatin-based chemotherapy. RESULTS: Review treatment-related toxicity for those patients receiving adjuvant chemotherapy (n = 97) or chemotherapy for recurrent disease (n = 83) showed no cases of acute cardiovascular toxicity. The median follow-up period after study enrollment was 5.1 years; 459 questionnaires were mailed and 270 were returned. The percent return was equal among the observed adjuvant and recurrent groups (59%, 54%, and 64%). There was a significant increase in the incidence of extremity paresthesias in the two groups receiving chemotherapy. Fatal myocardial infarction was reported in two patients in the observation group and one nonfatal infarction was reported in the adjuvant treatment group. No patient in any group reported an incidence of stroke. Three patients in the observation group and one patient in the recurrent group experienced a thromboembolic event. CONCLUSION: Despite sporadic case reports suggesting a causal association between chemotherapy for testicular cancer and acute vascular events, this retrospective analysis provides no evidence of an increased risk for subsequent cardiovascular disease in this patient population.

Acute Disease

Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy.

Two double-blind, crossover trials comparing the antiemetic effectiveness of nabilone, a new synthetic cannabinoid, with that of prochlorperazine were conducted in patients with severe nausea and vomiting associated with anticancer chemotherapy. Of 113 patients evaluated, 90 (80 per cent) responded to nabilone therapy, whereas only 36 (32 per cent) responded to prochlorperazine (P less than 0.001). Complete relief of symptoms was infrequent, occurring only in nine patients (8 per cent) given nabilone. When both drugs were compared, both nausea (P less than 0.01) and vomiting episodes (P less than 0.001) were significantly lower in patients given nabilone. Moreover, patients clearly favored nabilone for continued use (P less than 0.001). Predominant side effects noted by patients were similar for both agents and included somnolence, dry mouth and dizziness but were about twice as frequent and more often severe in patients receiving nabilone. In addition, four patients (3 per cent) taking nabilone had side effects (hallucinations in three, hypotension in one) that required medical attention. Euphoria associated with nabilone was infrequent (16 per cent) and mild.

Adolescent

Brain metastases in disseminated germinal neoplasms: incidence and clinical course.

From July 1973, to March 1978, 139 patients with disseminated germinal neoplasms were treated with a variety of combination chemotherapy regimens. Twenty-one patients (15.1%) exhibited evidence of brain metastases at some time during their course. Central nervous system spread occurred somewhat more frequently in patients with choriocarcinoma and yolk sac histologies, although all types were at risk. This was a major cause of morbidity and mortality. However, central nervous system spread almost always occurred in patients with systemic relapse and thus did not affect overall survival. We have yet to identify a subgroup who potentially could benefit from prophylactic central nervous system therapy.

Antineoplastic Agents

Cisplatin, bleomycin, and vinblastine combination therapy of testicular tumors: an analysis.

A combination regimen consisting of cisplatin, bleomycin, and vinblastine was evaluated in 86 patients with metastatic testicular tumors. Prior therapy included surgical resection of primary tumor (84 patients), radiotheapy (21 patients), chemotherapy (33 patients). Thirteen patients received prior bleomycin and vincristine or vinblastine. Of 80 evaluable patients 51 achieved complete response (CR) and 26 achieved partial response (PR), for an overall response rate 96.5%. There was no significant difference in response rates or survival with respect to prior therapy, sites of metastatic lesions, and tumor histology. The median survival time was not reached in an observation period of 44+ months. Sixty patients were alive 11+--44+ months, and 57 of these were free of disease. Thirty-two of the 60 patients (53%) had a survival time greater than 20 months. Toxicities included nephrotoxicity (18 patients) leukopenia, (69 patients), thrombocytopenia (nine patients), and anemia (56 patients). Bleomycin-induced pulmonary toxicity was fatal in one patient. Other toxicities included nausea and vomiting, stomatitis, fever, alopecia, and neurological effects.

Adolescent

cis-Platinum combination chemotherapy of bladder cancer: an update.

The combination of cis-platinum (DDP), adriamycin, and 5-fluorouracil was evaluated in 44 patients with advanced urothelial cancer, 39 of whom were evaluable for response. There were 18 partial remissions (46.2%) and no complete responses. Remissions were clinically meaningful, but of short duration. Four patients had bulky pelvic disease that was made resectable by chemotherapy, but none of these patients remained disease-free. These results are not superior to that expected from DDP as a single agent. In addition, there appears to be little or no survival benefit associated with chemotherapy. DDP represents an advance in the treatment of bladder cancer, but additional active agents and innovative approaches are needed.

Adult

Extraskeletal Ewing's sarcoma. Histologic and ultrastructural observations in three cases.

The histologic and ultrastructural morphology of three cases of Ewing's sarcoma of soft tissue are described and the fine structural features of extraskeletal Ewing's sarcoma are compared to those of similar round-cell tumors that are considered in the differential diagnosis. By light microscopy, these tumors are indistinguishable from Ewing's sarcoma of bone. Ultrastructurally, the salient features are also comparable to Ewing's sarcoma of bone and include: 1) absence of surface modifications; 2) cell-contact sites in the form of small thickenings of apposed membranes and large desmosome-like specializations; 3) undifferentiated cytoplasm usually containing abundant glycogen and occasionally nonspecific microfilaments; 4) significant variation in shape and irregularity of nuclear profiles. The ultrastructural features of extraskeletal Ewing's sarcoma are sufficiently distinctive to allow separation from from other small-cell malignant neoplasms in the majority of cases.

Adult

Chemotherapy of disseminated testicular cancer.

Dramatic improvements have been made in recent years in treatment of disseminated testicular cancer. Germ-cell neoplasms, even when advanced, are potentially curable by modern chemotherapy. Although disseminated testicular cancer is a rare disease, it is highly treatable, and primary physicians, internists and urologists should have some knowledge of its management.

Bleomycin

Long term effect of cis-diamminedichloride platinum (CDDP) on renal function and structure in man.

To examine CDDP induced nephrotoxicity in patients with testicular carcinoma, we measured renal function prior to therapy and at six month intervals for twelve months in fifteen patients and twenty-four months in seven patients. CDDP was given iv at 20 mg/M2 per day for five days at three week intervals. Eight patients received three courses, four received four courses and three received more than four courses. The mean creatinine clearance +/- SD prior to treatment was 112 +/- 12 ml/min. By six months, it had decreased to 68.5 +/- ml/min (p less than 0.01) and it remained at that level. Plasma creatinine and blood urea nitrogen increased significantly. Subjects receiving other potential nephrotoxins in addition to CDDP developed a greater decrease in creatinine clearance (p less than 0.05). Proteinuria and functional tubular disturbances were not observed. Microscopic features were characterized by hydropic degeneration of the renal tubular epithelium, thickened tubular basement membranes and mild interstitial fibrosis. Electron microscopy revealed phagolysosomes filled with flocculent material. CDDP resulted in a permanant, nonspecific renal injury in our patients. Although the renal injury has remained subclinical, future courses of CDDP may lead to clinically important chronic renal failure.

Adolescent

Improved management of nonseminomatous testis tumors.

Two contributions to the management of nonseminomatous germinal cell (NSGC) tumors of the testis are reviewed. First, a midline technique of extended retroperitoneal lymph node dissection (RPLND) has been developed allowing good access to both renal suprahilar zones as well as the traditional hilar and infrahilar areas. This has been employed at Indiana University Medical Center for staging patients with embryonal carcinoma or teratocarcinoma of the testis who had negative preoperative chest tomography. Of 58 consecutive patients from 1965-1975, 30 were Stage A and 28 Stage B. Thirty of 30 Stage A patients survived (100%) and 24 of 28 (86%) operated Stage B patients survived, for an overall survival of 54/58 (93%). The second contribution relates to development of a new combination chemotherapy protocol for Stage C disease. Preoperative Stage C lesions are treated with Platinum, Velban and Bleomycin (PVB). Those who achieve clearance of pulmonary tumors but who have anatomic or serologic evidence of persistent retroperitoneal tumor after PVB chemotherapy are later treated with RPLND. Six of 12 such patients have been rendered tumor free and now enjoy complete remission. Furthermore, 33 of 50 (66%) patients with disseminated Stage C disease achieved initial complete remission using this drug combination. Twenty-six remain in continuous complete remission with no evidence of disease from 2 to 4 years. Seven are alive, in partial remission, and 17 are dead. Improving chemotherapy opens alternative methods of managing advanced testis cancer.

Antineoplastic Agents

The effects of prior exposure to bleomycin on the incidence of pulmonary toxicities in a group of patients with disseminated testicular carcinomas.

The incidence of pulmonary toxicities in 12 patients with prior exposure to bleomycin (BLM) was compared to the incidence of pulmonary toxicities in a matched group of 73 patients with state II or IV testicular carcinomas treated with a regimen containing vinblastine, bleomycin, and cis-diamminedichloroplatinum. The comparison demonstrates that prior exposure to bleomycin constitutes a significant risk factor and that the risk is additive; ie, prior doses should be added to current doses to determine the cumulative dose-related probablity of development of pulmonary toxicities.

Adolescent

Combined therapy for small cell undifferentiated carcinoma of the lung.

Fifty-eight patients with small cell lung cancer were treated from September, 1974, to March, 1976, with combined chemotherapy and radiotherapy. Surgical resection of the lung lesion was performed in three patients, and a number of surgical diagnostic methods were carried out in the remaining patients with unresectable of disseminated lesions. Nineteen patients were from the Veterans Administration Hospital and 39 from Indiana University Medical Center. The median Karnofsky performance status was 60. Thirty-nine patients had extensive disease, and 19 had disease limited to the chest and supraclavicular area. All patients received chest radiotherapy and prophylactic whole brain radiation. Adriamycin, cyclophosphamide, and vincristine were given on day 1 and continued every 3 weeks. There were 27 (48 percent) partial remissions of a median duration of 26 weeks. There were 25 patients (43 percent) with complete remission. The median survival for the entire group was 51 weeks. Six of 58 patients (10 percent) are alive and disease free from 24 to 38 months after treatment. Six of 19 patients with limited disease (32 percent) are presently alive and disease free. This includes one patient in whom surgical resection was performed. Combined therapy influences favorably the prognosis of small cell cancer of the ling, expecially in those patients with limited disease and favorable performance status.

Adult

Long-term results in combined-modality treatment of small cell carcinoma of the lung.

Fifty eight patients with small cell carcinoma of the lung were treated with a combined-modality regimen: chemotherapy with adriamycin, cyclophosphamide, and vincristine; BCG immunotherapy; radiotherapy to the lung primary and prophylactic cranial irradiation. Ninteen patients had limited disease, and 39 had extensive disease. There were 27 (48%) partial remissions and 23 (41%) complete remissions, and median survival was 51 wk. Initial performance status and extent of disease had a definite effect on survival. Only 1 patient developed CNS metastases on prophylactic cranial irradiation. Five of 19 patients (26%) with limited disease remain alive and in complete remission at 26-45+ mo. It is becoming clear from this and other recent studies that we can significantly prolong median survival in small cell lung cancer. However, even more important is the fact that limited-extent small cell lung cancer may be a potentially curable disease.

Adult