Teniposide in metastatic renal and bladder cancer: a Southwest Oncology Group Study.
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Carcinoma, Renal Cell↗
Biomedical subjects
R M Bukowski
Publications and source records attributed to R M Bukowski.
Phase I trial of intraperitoneal chemotherapy with 5-fluorouracil and citrovorum factor.
A Phase I trial of intraperitoneally administered 5-FU and citrovorum factor was performed in eight patients with a variety of malignancies. Both drugs were given according to a single weekly dose schedule in a volume estimated to be 2000 cc, including residual ascites. Citrovorum factor 50 mg was given first, immediately followed by 5-FU 1000-3400 mg, according to a dose-escalating schedule. Myelosuppression proved to be the dose-limiting toxicity, though mucositis, diarrhea, nausea, and abdominal pain were also produced. Six patients failed to respond to therapy. One patient with malignant mesothelioma showed a significant decrease in the production of malignant ascites and a transient conversion of peritoneal fluid cytologies from positive to negative, while a second patient with pancreatic cancer showed conversion of peritoneal fluid cytologies from positive to negative and demonstrated an objective partial response of an hepatic metastasis. Dosage adjustment according to body surface area would seem indicated by the toxicity data, with a 5-FU dose of 1200 mg/m2 body surface area and citrovorum factor 50 mg/m2 being recommended for Phase II trials of this combination of drugs given according to this weekly schedule.
Antineoplastic Combined Chemotherapy Protocols↗
Erdheim-Chester disease. Case report and review of the literature.
Erdheim-Chester disease is a distinctive pathologic and radiographic entity characterized by bilateral, symmetric sclerosis of the metaphyseal regions of long bones and infiltration of foamy, lipid-laden histiocytes. Clinically, it ranges from an asymptomatic, focal process to a fatal, systemic disease. All previously reported cases of Erdheim-Chester disease are reviewed and a new case with diabetes insipidus, partial hypopituitarism, histiocytic skin lesions, and retro-orbital tumors is presented. An 11-year follow-up reveals progression from a benign, limited process to a progressive, systemic disease. Patients with Erdheim-Chester disease show markedly disparate clinical courses and some features similar to Hand-Schüller-Christian disease. They need careful monitoring and further attempts at treatment.
Adult↗
Intra-arterial chemotherapy as an adjuvant to surgery in transitional cell carcinoma of the bladder.
Regional chemotherapy with intra-arterial cis-platinum and doxorubicin as an adjuvant to total cystectomy and urinary diversion has been evaluated in a phase I to II study. In the first 17 patients chemotherapy consisted of 40 to 75 mg. per m. cis-platinum intra-arterially during 30 minutes, 30 to 40 mg. per m. doxorubicin intra-arterially during 60 minutes (11 patients) or 12 hours (6 patients) and 400 to 500 mg. per m. cyclophosphamide intravenously. The remaining 8 patients received 70 to 100 mg. per m. cis-platinum intra-arterially during 30 minutes. Intra-arterial chemotherapy was administered through a percutaneous catheter placed in the hypogastric artery before each course. Courses were repeated at 4-week intervals. A total of 25 patients received 58 courses (median 2 per patient). Clinical stages of disease in the patients entering the protocol were T3aNxMo (8), T3bNx-2Mo (12) and T4a-bNxMx-1 (5). Clinical response was assessed in 24 of 25 patients: 6 achieved a complete clinical response, 12 had a partial response and 7 had no response. Of 25 patients 16 underwent total cystectomy and urinary diversion with pathological staging as follows: ToNoMo in 3, T1NoMo in 1, T3aNoMo in 5, T3bNo-2Mo in 6 and T4NoMo in 1. Intra-arterial chemotherapy can produce a complete pathological response in patients with locally advanced bladder cancer and is tolerated well by most patients.
Aged↗
Gastric epithelial atypia associated with hepatic arterial infusion chemotherapy. Its distinction from early gastric carcinoma.
Hepatic arterial infusion chemotherapy (HAIC) for metastatic colonic carcinoma has been associated with gastric ulceration and marked epithelial atypia which may be mistaken for carcinoma. The authors reviewed the gastric histopathologic features of seven patients who developed gastric ulcers following HAIC and compared them with 20 examples of "early" gastric carcinoma. The seven patients had primary colonic carcinomas with hepatic metastases; each had received combination chemotherapy with mitomycin C and 5-fluorouracil via percutaneously placed hepatic arterial catheter. The gastric ulcers became clinically apparent 10 to 45 days after initiation of the final course of HAIC, usually heralded by severe epigastric pain. Based on the authors' observations, histologic features which are indicative of HAIC-associated atypia rather than carcinoma include: preservation of mucosal architecture; atypia accentuated in the basilar gastric glands; bizarre atypia with cellular enlargement exceeding that seen in carcinoma; preservation of a low nuclear-cytoplasmic ratio; cytoplasmic eosinophilia with vacuolization; few or no mitotic figures; cytologic resemblance to radiation effect; similar atypia within fibroblasts and endothelial cells; and absence of intestinal metaplasia in adjacent gastric epithelium.
Adenocarcinoma↗
Magnetic resonance with marked T2-weighted images: improved demonstration of brain lesions, tumor, and edema.
The object of this study was to determine the sensitivity of magnetic resonance (MR) for imaging intracranial lesions with heavily T2-weighted images compared with that of computed tomographic (CT) and T1-weighted images. Fifty-five patients with known intracranial pathology consisting of primary neurogenic tumors, brain infarcts, demyelinating disease, and metastases were studied by MR and CT. Patients were studied with either 0.6 or 1.5 T systems with T1- and T2-weighted radiofrequency pulse sequences. The heavily T2-weighted images were found to be superior to the T1-weighted images in terms of sensitivity, with 168 lesions found versus 86 by CT and 104 by T1-weighted imaging.
Brain Edema↗
Immunologic studies of peripheral blood lymphocytes and lymph nodes in Hodgkin's disease. A preliminary report.
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Adult↗
Retroperitoneal malignancies several years after initial treatment of germ cell cancer of the testis.
Three patients (aged 56, 40, and 38 years, respectively) presenting with large retroperitoneal masses 10 to 18 years after prior orchiectomy for testicular neoplasms (seminoma and embryonal carcinoma) are presented. Despite aggressive chemotherapy in all three patients and surgical excision of the tumor in two, two of the men subsequently died 11 to 16 months after initial diagnosis of the retroperitoneal tumors, and one is living with the disease. Theoretic etiologic mechanisms for the development of late retroperitoneal tumors in these men are discussed, including (1) metastatic disease from a second primary tumor in the remaining testicle, (2) a primary extragonadal retroperitoneal tumor, and (3) delayed transformation of metastatic teratomatous retroperitoneal tumor from the original primary into malignant neoplasm.
Adult↗
Hepatic artery infusion of 5-fluorouracil and mitomycin C in cholangiocarcinoma and gallbladder carcinoma.
Eleven patients with histologically proven cholangiocarcinoma and gallbladder carcinoma were treated with hepatic artery infusion (HAI) of 5-fluorouracil (5-FU) and mitomycin C (Mito-C). Catheters were placed percutaneously through the femoral artery. The schedule used was 5-FU 1200/mg/m2/day given as a continuous infusion for 4 days, plus Mito-C 6 mg/m2 on days 1 and 4. Courses were repeated every 4 weeks. Complete responses (CR) occurred in one patient (9%), and partial response (PR) occurred in six patients (55%). Median survival for all patients from the start of the first treatment was 12.5+ months. Median duration of the response was 3.0 months. Median survival of the patients with gallbladder carcinoma was 12.5 months, and for patients with cholangiocarcinoma has not yet been reached. Drug toxicity was mild, and morbidity of the HAI was minimal. Further trials of chemotherapy in these two neoplasms are warranted.
Adenoma, Bile Duct↗
T cell lymphoma occurring in Sjögren's syndrome.
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Antibodies, Monoclonal↗
Combination chemotherapy for metastatic carcinoma of the ampulla of Vater--report of three cases.
Three patients with metastatic carcinoma of the ampulla of Vater received celiac artery infusion of 5-fluorouracil, adriamycin, mitomycin-C, and streptozotocin followed by intravenous administration of the same combination. In two patients with measurable disease, one partial (6.0 months) and one complete response (16.0 + months) occurred. Two out of three patients remain alive at 30.0+ and 21.0+ months. Carcinoma of the ampulla of Vater may be a neoplasm responsive to combination chemotherapy.
Aged↗
Chemotherapy trials in malignant pheochromocytoma: report of two patients and review of the literature.
Two patients with metastatic pheochromocytoma received chemotherapy with 5-fluorouracil, cyclophosphamide, and streptozotocin. A biochemical response occurred in one instance. A review of the literature and the results in the reported patients indicate cyclophosphamide and/or streptozotocin may have activity in this neoplasm.
Adrenal Gland Neoplasms↗
5-Fluorouracil and folinic acid: a Phase I-II trial in gastrointestinal malignancy.
Fifty-one patients with metastatic adenocarcinoma received Folinic Acid (FA) combined with 5-Fluorouracil (5FU) in a Phase I-II clinical trial. Two different schedules were used: (a) bolus infusion--5FU 7-12 mg/kg/d I.V. d1-5, FA 1.6 mg/kg/d I.V. d1-5; (b) continuous infusion--5FU 600-1200 mg/m2/d I.V. d1-4, FA 60 mg/m2/d I.V. d1-4. Mucositis and myelosuppression were dose-limiting, with recommended dose levels of 5FU for further trials being 10 mg/kg/d I.V. d1-5 and 1000 mg/m2/d I.V. d1-4 on the bolus and continuous infusion schedules, respectively. Forty-one evaluable patients with measurable disease were treated. Thirty-six had metastatic colorectal carcinoma, and 14/36 patients responded (CR-1, PR-13), including responses in three patients who had previously failed 5FU treatment alone. In the two patients with unknown primary sites and three with gastric cancer, no response were seen. 5FU and FA have activity equivalent to 5FU alone, and the responses in patients receiving prior 5FU suggest it may be superior. The possibility that toxicity may be enhanced does exist. Further trials of these two agents are warranted.
Adenocarcinoma↗
Chlorozotocin: results in colorectal carcinoma treated with high and low doses. A Southwest Oncology Group study.
Clorozotocin was evaluated in patients with advanced colorectal cancer at 225 mg/m2 every six weeks in 14 patients with no prior treatment, at 200 mg/m2 in 43 patients with normal tolerance of prior chemotherapy, and at 100 mg/m2 in 38 patients with extensive or poorly tolerated prior therapy. Median survival for the respective groups was 192, 107 and 79 days; these differences are best explained as a function of performance status. Partial response was reported for one patient, 15 had disease stabilization and two had improvement short of partial remission. Myelotoxicity was acceptable at all doses, with thrombocytopenia being dose limiting at 225 mg/m2. Four patients developed azotemia during or after chlorozotocin treatment. Chlorozotocin has minimal activity against colorectal carcinomas and no dose-response relationship is evident.
Adenocarcinoma↗
Phase-I trial of UltrapureTM human leukocyte interferon in human malignancy.
A phase-I trial of UltrapureTM human leukocyte (alpha) interferon was performed, in which 15 patients were treated according to a dose-ranging protocol. Five patients were treated at each of these dosage levels: 2 X 10(6) IU/dose, 9 X 10(6) IU/dose, and 15 X 10(6) IU/dose. Doses were given on days 1-5 and 8-12 of a 28-day study period. Serial NK-cell assays were performed in all patients, and failed to show consistent effects referable to treatment. Serum interferon levels were assayed on one patient at the 9 X 10(6) IU and one patient at the 15 X 10(6) IU dose level. In both cases, a significant interferon titer (greater than or equal to 160) was detected in the serum, and this persisted for as long as 12 h. Fever, malaise, and myalgias were associated with therapy. The dose-limiting toxicity was a dose-related leukopenia, with median white blood cell nadirs of 6,500/mm3 (3 X 10(6) IU/dose), 3,200/mm3 (9 X 10(6) IU/dose), and 1,800/mm3 (15 X 10(6) IU/dose) being produced. One patient died in ventricular fibrillation while suffering chest pain after receiving 5 days of treatment at the 15 X 10(6) IU/dose level. Three patients showed minor responses, insufficient to be called partial responses, in association with interferon therapy. We conclude that dose-limiting leukopenia occurs with this schedule of administration of UltrapureTM human leukocyte interferon at 15 X 10(6) IU/dose.
Adult↗
Successful combination chemotherapy for metastatic parathyroid carcinoma.
A 54-year-old patient with metastatic parathyroid carcinoma and severe hypercalcemia refractory to conventional treatment was treated with chemotherapy consisting of fluorouracil, 500 mg/sq m intravenously (IV) daily for four days (24-hour infusion), cyclophosphamide, 500 mg/sq m IV daily for four days, and dacarbazine (imidazole carboxamide), 200 mg/sq m IV daily for four days. Complete objective and partial biochemical responses were noted, with the response duration being 5.0 + months. The toxic reaction was moderate and predominantly gastrointestinal.
Antineoplastic Combined Chemotherapy Protocols↗
Randomized trial of 5-fluorouracil and mitomycin C with or without streptozotocin for advanced pancreatic cancer. A Southwest Oncology Group study.
A prospective randomized trial comparing streptozotocin, mitomycin C, and 5-FU (SMF) with mitomycin C and 5-FU (MF) in patients with advanced pancreatic cancer was performed. In patients with measurable disease the response rates were 34% (19/56) to SMF, and 8% (5/60) to MF (P = 0.009). Median survivals were similar, however, 18 versus 17 weeks (P = 0.356). Median survival of patients responding to chemotherapy was 33 weeks, and for nonresponders it was 17 weeks (P = 0.002). In patients with nonmeasurable disease, median survivals were 21 weeks (SMF) and 18 weeks (MF) (P = 0.797). Patients surviving greater than or equal to 48 weeks, however, appeared to be increased in the SMF arm (14 patients) compared to the MF (7 patients). Toxicity was moderate for both regimens, with SMF having greater gastrointestinal and renal toxicity. Chemotherapy with SMF appears to produce objective responses in patients with pancreatic cancer, but does not improve survival compared to MF.
Adult↗
Randomized controlled trial of transfer factor in Stage II malignant melanoma.
Thirty-six patients with Stage II malignant melanoma were randomized to no further therapy or transfer factor (TF) following surgical removal of all evident disease. Eighteen patients received TF, and 18 were in the surgery only group. Median disease-free intervals were 12.0 and 10.0 months, and survival, 40.8 and 27.0 months, respectively. Nine TF patients and four control patients remain alive. These differences were not statistically significant, and no adjuvant effect of TF could be demonstrated.
Adult↗