Biomedical subjects
Publications and source records attributed to R C Watson.
4'Epi-adriamycin in doses of 85-110 mg/m2 I.V. Q3W was given to 20 patients with advanced bidimensionally measurable hypernephroma. Forty-five doses were administered, with 10 patients receiving 3-7 doses. Myelosuppression (WBC nadir 2600 cells/mm3, range 1000-3400) occurred in 63% and thrombocytopenia in 16% of cases. There was no objective response in 19 adequately treated cases.
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Vinblastine sulfate 0.10-0.15 mg/kg IV every week, was given to 37 patients with bidimensionally measurable, metastatic transitional cell carcinoma of the urothelial tract. Twenty-eight patients, the majority of whom had received extensive prior chemotherapy, had an adequate trial and five (18%; 95% confidence limits, 3-33%) achieved a partial remission (greater than 50% decrease in tumor size) of 2-5 months' duration. Responding sites included lung and nodal metastases. Toxicity, primarily leukopenia, was mild to moderate. The 18% response rate obtained in heavily pretreated cases suggests that vinblastine sulfate has some efficacy in the treatment of patients with advanced urothelial tract tumors.
There were 60 patients at our cancer center who underwent serum tumor marker studies (beta subunit of human chorionic gonadotropins and alpha-fetoprotein) and pedal lymphangiography before retroperitoneal lymph node dissection. Surgical stage II cases were divided according to tumor, node and metastasis staging. Beta-human chorionic gonadotropin and/or alpha-fetoprotein was elevated in 9 per cent (1 of 11) and the N1 cases, 36 per cent (5 of 14) of the N2A cases, 50 per cent (13 of 26) of the N2B cases and 89 per cent (8 of 9) of the N3 cases. Lymphangiography was positive or suspicious in 9 per cent (1 of 11) of the N1 cases, 36 per cent (5 of 14) of the N2A cases, 46 per cent (12 of 26) of the N2B cases and 56 per cent (5 of 9) of the N3 cases. Serum tumor markers and lymphangiography combined suggested lymph node metastases in 18 per cent (2 of 11) of the N1 cases, 50 per cent (7 of 14) of the N2A cases, 73 per cent (19 of 26) of the N2B cases and 100 per cent (9 of 9) of the N3 cases. We conclude that tumor markers and lymphangiography measurements are equally effective in the diagnosis of retroperitoneal lymph node metastases and that diagnostic accuracy is enhanced significantly by combining these 2 modalities. Retroperitoneal lymph node dissection remains the most reliable staging procedure. Reports of the accuracy of clinical staging should be correlated with subcategories of stage II disease.
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Forty-nine patients with transitional urothelial tract tumors received methotrexate: 0.5-1.0 mg/kg I.V. Q W (40 patients) or 250 mg/M2 in a 2-hour infusion with citrovorum factor rescue 24 hours later (nine patients). Eleven (26%, 95% confidence limits 13-39%) of 42 patients with bidimensionally measurable metastases achieved partial remission. Most responses occurred within 2-3 weeks and persisted for a median duration of six months (range, 2-20). Response rates were increased to 38% (6/16 patients, 95% confidence limits 18-65%) in patients who had no prior chemotherapy, and a 90-100% performance status (50, 5/10 patients, 95% confidence limits 22-78%) compared with 19% (5/26, 95% confidence limits 8-37%) in patients who had prior chemotherapy and a less than or equal to 80% performance status (19%, 6/32 cases, 95% confidence limits 9-32%). Toxicity included mucositis and myelosuppression. A review of the literature coupled with the present data suggest that methotrexate is as active as cisplatin in the treatment of patients with advanced urinary bladder cancer.
Pelvic lymphadenectomy is used widely for staging prostatic or bladder carcinoma. In 9 of 187 patients (4.7 per cent) who underwent bilateral pelvic lymphadenectomy for urologic cancer pelvic lymphocele diveloped. The management of these patients is presented along with review of causes, clinical features, diagnosis, and treatment. Pelvic CT scan is a noninvasive modality which aids in the diagnosis of this complication. Minidose heparin used for prophylaxis of thromboembolic complications may increase lymphocele formation.
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Neocarzinostatin (NCZ), a new antitumor antibiotic, was administered to 19 patients with bladder cancer, 16 patients with prostatic cancer, and 3 patients with hepatoma. All patients had objectively measurable metastatic lesions including 21 with palpable nodes or subcutaneous nodules, 10 with pulmonary nodules as demonstrated by chest x-ray, 4 with malignant hepatomegaly, and 3 with bidimensional pelvic masses as demonstrated by CT scanning. Sixty-five courses of NCZ were administered via an intravenous bolus daily for five days with dosages ranging from 1500 to 3000 U/m2. Immediate toxicity was not dose-limiting except for 1 episode of anaphylaxis and 1 of acute renal failure. Myelotoxicity was delayed, dose-dependent, noncumulative, and dose-limiting. Thrombocytopenia was prolonged or irreversible in 5 cases. The maximally tolerated dose was 2750 U/m2. One patient with NCZ-associated pulmonary fibrosis and 1 with biopsy-proven hepatitis are discussed in detail. Neocarzinostatin demonstrated minimal therapeutic activity (1 partial remission) in patients with bladder cancer. There was no response in patients with prostatic cancer or hepatoma.
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Cis-diamminedichloride platinum II (DDP), 50--70 mg/m2 iv, q 3w was administered to 25 patients with Stage D adenocarcinoma of the prostate. Since the assessment of tumor regression in a disease-oriented phase II study demands a clear end-point of response, case selection was restricted to patients who had objectively measurable lesions, i.e., nodes, skin, lung, and liver metastasis. Partial remission occurred in 3 (12%) and stabilization of disease in 1 patient. Responders lived 53 weeks vs. 20 weeks for non-responders. In the dosage and schedule used in this protocol, DDP was not an active agent in the treatment of prostatic cancer. Various patient characteristics are examined and correlations made between remission rates and survival in this study vs. 4 other response schemata. A critical analysis of patient selection, "lead time" -- diagnosis to chemotherapy, and the definitions of the terms "measurable" lesions, "evaluable" parameters, "objective response", stabilization of disease and response criteria employed in the 4 schemata are also discussed.
Fifty cases of lower extremity tumors examined with computed tomography were reviewed. Of the 50 cases, 41 had gross pathologic correlation, either by enbloc resection (26) or by amputation (15). Important information regarding size, location, definition, and anatomic relation of tumors to vital structures (neural, vascular, and osseous) may be ascertained by this means with great accuracy. Localization of vessels by intravenous infusion of contrast material during the scan, or after arteriography with intraarterial contrast infusion, is found to enhance such evaluation. This information is particularly important where the feasibility of en-bloc resection is being evaluated.
Thirteen patients were found to have giant-cell tumors during a study of 91 primary tumors of the sacrum. This tumor was second only to the chordoma in incidence. Giant-cell tumor is by far the commonest benign lesion of the sarcrum, yet it has a bad prognosis. Recurrences occurred in seven patients and five died of disease or a complication. All were histologically benign when first seen, but one developed a malignant giant-cell tumor and died within two years, and one developed a radiation-induced sarcoma 10 years following treatment. Computed tomography in two recent patients proved to be the most valuable single examination. Arteriography is helpful in showing the degree of vascularity of the tumor and the exact position of the large vessels, particularly important when surgical resection is planned.
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