Biomedical subjects

D L Trump

Publications and source records attributed to D L Trump.

At least 73 records · Page 4Linked to original sources

PubMed1992

Hypercalcemia and neuroendocrine carcinoma of the prostate: a report of three cases and a review of the literature.

PURPOSE: Hypercalcemia is a rare complication of prostate cancer, and no definite association with any histologic subtype of prostatic malignancy has been documented. We have recently seen three patients who developed hypercalcemia in the setting of prostate cancer. All had neuroendocrine carcinoma of the prostate (NCPs), which prompted an exploration of the potential association of hypercalcemia with NCP. DESIGN: An extensive review of literature published in the English-language was conducted to identify cases of hypercalcemia associated with prostate cancer and well-documented cases of NCP. RESULTS: We found 17 reported cases of hypercalcemia clearly associated with prostate cancer and a total of 61 cases of well-documented NCP. Including our cases, 11 of the 20 reported cases of hypercalcemia associated with prostate carcinoma were in patients with neuroendocrine carcinomas. CONCLUSION: Hypercalcemia in the setting of prostate cancer should prompt a search for unusual histologies.

Adenocarcinoma↗

PubMed1992

High-dose carboplatin and etoposide with autologous bone marrow transplantation in refractory germ cell cancer: an Eastern Cooperative Oncology Group protocol.

PURPOSE: A phase II trial was undertaken to assess the feasibility, toxicity, and efficacy of high-dose carboplatin and etoposide with autologous bone marrow transplantation in patients with relapsed or refractory germ cell tumors. PATIENTS AND METHODS: Forty patients with recurrent germ cell cancer received carboplatin 500 mg/m2 and etoposide 400 mg/m2 given at 7, 5, and 3 days before marrow infusion. Autologous marrow infusion (day 0) was accomplished using one half of the bone marrow harvested before chemotherapy. Patients who achieved a complete or partial response with the first cycle of treatment received a second identical cycle of chemotherapy followed by infusion of the remaining cryopreserved bone marrow. RESULTS: Objective responses were obtained in 17 of the 38 patients (45%) assessable for response, including eight partial and nine complete remissions. Five of these patients remain in continuous complete remission with minimal follow-up of 1 year. Toxicity encountered was primarily hematologic, and five patients (13%) died of treatment-related complications. Significant toxicities often seen with high-dose cisplatin (ototoxicity, neurotoxicity, and renal toxicity) were manageable in this regimen of high-dose carboplatin. CONCLUSIONS: This trial confirms the curative potential of high-dose carboplatin and etoposide in highly refractory germ cell cancer.

Adolescent↗

PubMed1992

Metastatic bladder cancer. Natural history, clinical course, and consideration for treatment.

Patients with metastatic transitional-cell carcinoma of the bladder have a poor prognosis with brief survival. Controversy exists as to the clonality of bladder cancer, as well as the natural history of muscle-invasive disease that subsequently becomes metastatic. Newer molecular biologic techniques may help us identify and understand the molecular changes involved in transforming normal urothelium into the malignant phenotype. In addition, newer chromosomal markers may enable us to determine the prognosis and the potential for progression to invasion and metastases. Additional work to find the optimum doses and dosing schedules and combinations of chemotherapeutic agents for metastatic transitional-cell carcinoma will be necessary before we can improve survival for all patients with this disease.

Antineoplastic Agents↗

PubMed1991

A phase I study of SR-2508 and cyclophosphamide administered by intravenous injection.

SR-2508, a less lipophilic ane neurotoxic analogue of the nitroimidazole, misonidazole, has exhibited significant chemosensitization properties in preclinical studies with alkylating agents. A phase I trial was carried out to assess toxicity and possible pharmacological interactions of the combination of short infusions of SR-2508 and cyclophosphamide (CP). Patients were randomly assigned to receive either CP alone followed in 3 wk by CP + SR-2508, or CP + SR-2508 followed by CP alone. All additional courses were CP + SR-2508. The maximum tolerated dose of the combination was determined by dose escalation of SR-2508 while the dose of CP remained fixed, initially 1.0 g/m2, and then a second maximum tolerated dose was determined with CP at 1.6 g/m2. One hundred seventeen evaluated courses were administered to 39 patients, the majority of whom had received prior treatment. Somewhat unexpectedly, reversible grade 4 granulocytopenia was the dose-limiting toxicity occurring in four of five evaluable first combination courses at level 6 (SR-2508, 11.3 g/m2; CP, 1.0 g/m2), the initial maximum tolerated dose. SR-2508 enhanced CP-induced myelosuppression as exhibited by the significant difference (p less than 0.001) between the 27 paired courses (CP versus CP + SR-2508) for WBC nadirs over levels 1 to 6. The neurotoxicity encountered was similar to that seen in past clinical trials, being reversible, mild, and usually peripheral in nature. There was one treatment-related death (neutropenic sepsis) on study. No other significant toxicity was seen. SR-2508 exhibited linear pharmacokinetics over the dose range studied. The SR-2508 area under the concentration-time curve increased linearly with dose (r = 0.858; p less than 0.001). No other parameters were dose related. Neither drug appeared to affect the pharmacokinetics of the other, and CP pharmacokinetic values were consistent with those from prior studies. Due to the interaction noted between the two agents and the preclinical data suggesting preferential enhancement of antitumor efficacy under this combination, phase II study appears warranted.

Adult↗

PubMed1991

A phase II study of taxol in patients with malignant melanoma.

Based on results of a phase I study demonstrating antitumor activity of taxol in patients with melanoma, 34 patients with documented metastatic melanoma received taxol, 250 mg/m2, as a 24-hours infusion, repeated every 21 days, in this phase II study. All patients received premedication with dexamethasone, diphenhydramine and cimetidine. Four patients experienced anaphylactic reactions and stopped treatment. Other significant toxicity of this drug included short-lived but severe neutropenia (less than 1,000/mm2) and peripheral neurotoxicity. Four of 28 evaluable patients demonstrated objective response (14%) (confidence interval, 4%-33%) including 3 complete responses and 1 partial response. Two complete responders are continuing at 25+ and 38+ months after achieving CR. Minor evidence of anti-tumor activity was noted in five additional patients. Taxol has significant activity in melanoma and should be further studied in combination with other agents in this disease.

Adult↗

PubMed1991

Complications of hepatic arterial infusion chemotherapy.

Chemotherapy by direct hepatic arterial infusion (HAI) results in reduction in tumor mass in a large percentage of patients. The authors reviewed records for 45 patients with metastatic cancer of the gastrointestinal tract who underwent HAI chemotherapy with floxuridine, administrated via an implanted pump. Twenty-seven of the 45 patients suffered complications, including gastrointestinal ulceration (18%), hepatitis (24%), sclerosing cholangitis (7%), and abscess (2%). The complication rates in this series were similar to those previously reported. The toxicity of HAI chemotherapy continues to limit its efficacy.

Aged↗

PubMed1991

Pharmacokinetic and pharmacodynamic analysis of fluorouracil during 72-hour continuous infusion with and without dipyridamole.

During a phase I trial of 3-day simultaneous continuous intravenous infusions of varying doses of fluorouracil (5FUra) and 7.7 mg/kg/d of dipyridamole, we examined the relationships between 5FUra dose and steady-state plasma concentration (Css) and the percentage reduction in WBCs, as well as the percentage frequency of stomatitis. The 5FUra was administered at doses ranging from 185 mg/m2/d times three to 3,600 mg/m2/d times three. In 42 patients, 86 cycles of 5FUra plus dipyridamole and 28 cycles of 5FUra alone were analyzed. The Css of 5FUra varied even within the same dose level. When patients receiving the same 5FUra dose were considered, the interpatient coefficient of variation of 5FUra Css in cycles of 5FUra plus dipyridamole was 23% +/- 4.2%. For courses of 5FUra alone, the coefficient of variation of 5FUra was 15.6% +/- 6.5%. When the occurrence of any degree of stomatitis was related to the Css 5FUra, with patients grouped in cohorts of 2-mumol/L increments, the following equations accurately described the frequency of stomatitis: for 5FUra plus dipyridamole, percentage frequency of stomatitis = 100(1-e-0.114Css), r2 = 0.88; for 5FUra alone, percentage frequency stomatitis = 100(1-e0.122Css), r2 = 0.80. When 5FUra dose was substituted for Css, these relationships were as follows: percentage frequency of stomatitis = 100(1-e-0.00031 [dose]), r2 = 0.85; and percentage frequency of stomatitis = 100(1-e-0.00051 [dose]), r2 = 0.80. When the relationship between the percentage reduction in WBC and Css 5FUra was examined, statistically significant relationships were also apparent: for 5FUra plus dipyridamole, percentage reduction in WBC = 100(1-e-0.085Css), r2 = 0.46; for 5FUra alone, percentage reduction in WBC = 100(1-e-0.060Css), r2 = 0.61. When 5FUra dose was substituted for Css, these relatinships were as follows: percentage reduction in WBC = 100(1-e-0.00023 [dose]), r2 = 0.40; percentage reduction in WBC = 100(1-e-0.00024 [dose]), r2 = 0.65. The relationship between either Css 5FUra or dose 5FUra and either stomatitis or myelosuppression were also well described by the modified Hill equation (J Theor Biol 20:171-201, 1968). These analyses indicate that it should be possible to develop therapeutic regimens wherein 5FUra is administered to achieve a targeted Css determined by the risk and severity of toxicity deemed acceptable.

Bone Marrow Diseases↗

PubMed1991

Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases.

One hundred sixty-five patients were randomized to receive either interferon alfa-n1 (Wellferon; Burroughs Wellcome Co, Research Triangle Park, NC) alone or with vinblastine. An initial six-cycle induction treatment consisted of interferon given at daily doses of 3, 5, 20, 20, and 20 x 10(6) U/m2 every 2 weeks. Vinblastine at a dose of 10 mg/m2 (later decreased to 5 mg/m2) was given on day 1 of alternate cycles. Toxicities were generally well tolerated. The overall response rate was 10% with no significant difference between treatment arms. Survival was also not significantly different for the arms. A small subset of patients (16) with metastases only to the lungs had a high complete response (CR) and partial response (PR) rate of 44%. Responses were durable, and overall survival of this group was much better than that of the other patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Phase I trial of 5-fluorouracil and dipyridamole administered by seventy-two-hour concurrent continuous infusion.

Forty-seven patients with advanced malignancies were treated with a concurrent 72-h continuous infusion of 5-fluorouracil (FUra) and dipyridamole. The FUra dose was escalated over the dose range of 185 to 3600 mg/m2/day for 3 days. Dipyridamole was administered in a fixed dose of 7.7 mg/kg/day for 3 days. A total of 155 courses of therapy were completed of which there were 31 paired courses of the combination and FUra alone, at the same dose of FUra and in the same patient. This was for purposes of analysis of pharmacokinetics and modulation of FUra toxicity by dipyridamole. Stomatitis was the dose-limiting toxicity experienced by patients entered into this trial. Myelosuppression was not a serious problem. Increasing FUra plasma concentration was associated with greater leukopenia and stomatitis. Dipyridamole did not appear to modulate the systemic toxicity of FUra. The pharmacokinetics of FUra were altered by the concurrent administration of dipyridamole. Dipyridamole promoted the total body clearance of FUra which resulted in lower mean steady-state FUra plasma concentrations when compared with courses of FUra alone administered at the same dose level. These differences were statistically significant over the course of the trial. For courses of the combination, FUra exhibited linear pharmacokinetics over the dose range studied. Total body clearance of FUra declined slightly at the higher dose levels, but the differences were not significant. For courses of FUra alone, total body clearance was significantly decreased above the dose level of 2300 mg/m2/day. At the maximal tolerated dose of FUra, 2300 mg/m2/day x3, mean steady-state FUra plasma concentration and total body clearance were 6.6 microM and 122 liters/h/m2, respectively, for courses of the combination. The corresponding pharmacokinetic parameters were 7.4 microM and 103 liters/h/m2 for courses when FUra was given alone. Further evaluation of the utility of this regimen and basis of these pharmacokinetic observations appear warranted.

Adult↗

PubMed1990

Psychological and mood disturbance associated with the diagnosis and treatment of testis cancer and other malignancies.

Eighty-seven men with testis cancer (TC) and 35 men with other cancers (OC) completed measures of mood (Profile of Mood States) and of personality and psychopathology (Millon Clinical Multiaxial Inventory). Effects of primary disease, phase of diagnosis and treatment, locoregional vs. cytotoxic treatment, age, and marital status on these measures were examined. TC patients appeared more distressed during treatment, particularly during cytotoxic as compared to locoregional treatment, than before or after treatment, and more distressed than OC patients. Being married appeared to buffer the stress of cancer and its treatment. Although treatment, particularly cytotoxic therapy, appeared to result in transient distress, results did not offer strong evidence that cancer and its treatment typically precipitate severe psychopathology.

Adaptation, Psychological↗

PubMed1990

A phase II trial of carboplatin (NSC 241240) in advanced prostate cancer, refractory to hormonal therapy. An Eastern Cooperative Oncology Group pilot study.

Twenty-nine patients with metastatic prostate cancer progressing after hormonal therapy (orchiectomy 19, diethylstilbestrol 10) and who had never received cytotoxic therapy were treated with carboplatin. Patients had good clinical performance status (66% PS 0,1) and adequate renal (creatinine less than 2.0 mg/dL) and bone marrow function. The standard dose of carboplatin administered was 400 mg/sq m. Seventeen patients received this dose and 12 either 320 mg/sq m or 250 mg/sq m based on reduced renal function or prior radiation. Five patients had bidimensionally measurable disease: one experienced a partial regression of cervical lymph node metastases of 97 days duration. Twenty-four patients had metastatic disease evaluable by clinical status, bone scan and acid phosphatase. In one patient greater than 50% reduction in number of abnormal areas of bone scan uptake occurred; 3 patients experienced improvement in clinical status; in no patient did an elevated prostate acid phosphatase return to normal. All patients entered on study have progressed and died: median time to progression was 94 days (6 to 625 days); median survival was 297 days (6-1152 days). The primary toxicity of carboplatin was myelosuppression. The median WBC and platelet nadirs after cycle one were 3150/cu mm and 93,000/cu mm, respectively. Dose escalations to grade 2 or greater myelosuppression were mandated. Twenty-six achieved at least grade 2 myelosuppression during carboplatin treatment. We conclude that carboplatin administered at this dose and schedule has no important activity in hormone refractory prostate cancer.

Bone Neoplasms↗

PubMed1990

Evaluation of carboplatin (NSC 241240) in patients with recurrent or metastatic renal cell carcinoma.

Eighteen evaluable patients with metastatic or recurrent renal cell carcinoma were treated with carboplatin. Fourteen patients received 400 mg/m2 as the initial dose, and four patients received reduced doses based on prior radiation therapy and/or elevated serum creatinine. No responses were seen. Median survival of these 18 patients was 8.3 months. Risk group status which previously has been identified as an important indicator of survival was predictive for survival in this study. Patients in the most favorable risk groups had a median survival of 21.2 months vs. 6.6 months for the most unfavorable risk groups. No lethal toxicities occurred with the administration of carboplatin; however, 66% of patients received doses of sufficient magnitude to cause severe or life threatening thrombocytopenia or anemia.

Anemia↗

PubMed1990

Randomized phase II evaluation of carboplatin and CHIP in advanced transitional cell carcinoma of the urothelium. The Eastern Cooperative Oncology Group.

A total of 83 patients with metastatic transitional cell carcinoma who had previously received no systemic therapy entered a randomized phase II evaluation of carboplatin and cis-dichloro-transdihydroxy-bis-isopropylamine platinum IV (CHIP), administered respectively at 400 and 270 mg./m.2 every 28 days. Among evaluable patients with measurable disease response rates were 3 of 22 (14%, 95% confidence interval 5 to 35%) for carboplatin and 4 of 25 (16%, 95% confidence interval 5 to 36%) for CHIP. Among 17 patients with evaluable but not measurable metastases (10 carboplatin and 7 CHIP recipients) there were no responses. Median survival for 64 evaluable patients was 4.8 months (5.0 months for carboplatin and 4.3 months for CHIP recipients). Independent factors prognostic for survival (p less than 0.01) were performance status (0 or 1 versus 2 or 3), liver metastases, prior radiation therapy and recent weight loss (p = 0.02). Multivariate analysis confirmed that a performance status of 2 or 3 and liver metastases were predictive of shorter survival. A total of 31% of the patients treated with carboplatin and 34% of those who received CHIP experienced severe or life-threatening myelosuppression. While the response rates with carboplatin and CHIP are modest, we believe that the characteristics of these agents indicate that they should be evaluated further.

Aged↗

PubMed1990

Perioperative methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) for poor risk transitional cell carcinoma of the bladder: an Eastern Cooperative Oncology Group pilot study.

A total of 18 patients with locally advanced transitional cell carcinoma of the bladder underwent 2 preoperative cycles of chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin followed by radical cystectomy and 2 postoperative cycles of chemotherapy. Radical cystectomy was performed in 17 of 18 patients (94%) with a pathological partial response in 3 (17%) and a pathological complete response in 2 (11%), for an over-all response rate of 28% (95% confidence limits 10 to 53%). At 23-month median followup 9 patients (50%) remained without evidence of recurrent disease, while 9 (50%) died of metastatic bladder cancer. Average relative dose intensity of all therapy given was 78%. Hematological toxicity was moderate, with no septic deaths or bleeding complications. However, 4 thromboembolic events occurred. While downstaging of the primary bladder tumor can occur with this perioperative schedule our results were not as impressive as some previously reported findings. The incidence of thromboembolic events is worrisome.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Biological and clinical effects of interferon-beta ser at two doses.

To assess biological response, therapeutic activity, and side effects, a randomized, double-blind trial of two doses of interferon-beta ser (IFN-beta ser), differing by 20-fold 4.5 and 90 x 10(6) units), was undertaken in 64 patients with metastatic renal carcinoma. Patients were treated intravenously with injections daily for 10 days with an 11-day rest before treatment was reinitiated. The trial confirmed the relatively good toleration of IFN-beta ser; in the first cycle only 4/63 patients had anorexia of moderate or greater severity. Median weight change over the duration on study was -1.5 kg; in the first cycle only 7% of patients had performance status decline greater than 1 level. Statistically significant changes (p less than 0.05) occurred in granulocytes, lymphocytes, calcium, cholesterol, alkaline phosphatase, and aspartate transferase (AST); however, except for AST, overall clinical differences in the two doses were not great. Of 60 patients evaluated, 1 developed neutralizing antibody. When assessed 24 h after IFN-beta ser at 4.5 x 10(6) units, significant (p less than 0.05) augmentation had occurred in beta 2-microglobulin, HLA-DR, and HLA-DQ expression on monocytes, 2',5'-oligoadenylate (2-5A) synthetase in peripheral mononuclear cells, and natural killer (NK) and K cells functional activity. Although the 90 x 10(6) unit dose also resulted in stimulation of these responses, little additional augmentation of biological response occurred at the higher dose. Except for a decline in monocyte HLA-DR expression, biological responses remained increased at both doses over the 10-day period of treatment. However, no objective regressions of metastatic disease occurred. In view of objective responses in metastatic renal carcinoma in other trials with IFN-beta ser, consideration should be given to alternative schedules.

2',5'-Oligoadenylate Synthetase↗

PubMed1990

Phase II trial of carboplatin in soft-tissue sarcoma.

As part of the Eastern Cooperative Oncology Group program for the assessment of new drugs in sarcomas, a Phase II trial of carboplatin was performed in patients who had received no more than one prior chemotherapy regimen. A total of 50 patients received either 400 mg/m2 or 320 mg/m2 depending on whether they had received prior radiotherapy. A response rate of 16% (95% confidence interval 6-32%) occurred in the 37 patients who had received doxorubicin as their only prior systemic therapy. Three of the six responses were complete and persisted for 7 to 34 months. In contrast none of the 13 patients who received carboplatin after initial progression on doxorubicin and subsequent progression on interferon alpha responded. The overall response rate was therefore 12% (95% confidence interval 5-24%). Toxicity was primarily hematologic, with 14 patients having Eastern Cooperative Oncology Group (ECOG) grade 3 toxicity and no grade 4 or 5 toxicities. In view of the number of complete responses, carboplatin should be studied further in untreated patients with advanced soft tissue sarcoma.

Adult↗

PubMed1990

Hypersensitivity reactions from taxol.

Taxol is an antitumor agent in clinical trial that has been shown to have activity against advanced ovarian carcinoma and melanoma. Hypersensitivity reactions (HSRs) have been one of the toxicities observed with administration of this drug. Of 301 patients treated, 32 patients have had definite (27 patients) or possible (five patients) hypersensitivity reactions to taxol. All but one patient had the reaction from the first or second exposure to this agent. Reactions occurred at a variety of doses and were characterized most frequently by dyspnea, hypotension, bronchospasm, urticaria, and erythematous rashes. Thirteen (41%) patients had received premedication designed to prevent such toxicity; nevertheless, they sustained HSRs. Prolonging the drug infusion appears to have somewhat reduced, but not obviated, the risk of HSRs. The cause (taxol itself or its excipient Cremophor EL; Badische Anilin und Soda-Fabrik AG [BASF], Ludwigshafen, Federal Republic of Germany) and the mechanism of these reactions to taxol are unknown. We provide guidelines to prevent or minimize such toxicity and treat reactions if they still occur.

Adult↗

PubMed1990

Interferon-alpha-n1 and continuous infusion vinblastine for treatment of advanced renal cell carcinoma.

Eighteen patients with advanced renal cell carcinoma were treated with human lymphoblastoid interferon (Wellferon) and continuous fusion vinblastine. All patients received vinblastine as a continuous infusion at a dose of 1.5 mg/m2/day on days 1 to 5. The interferon was given by daily intramuscular injections on days 1 to 10. Three patients were treated with a dose escalation scheme that reached a maximum daily dose by day 3 of 5 X 10(6) units/m2/day and that was then continued until day 10. Fifteen patients received 3 X 10(6) units/m2/day on day, 1, and 5 X 10(6) units/m2/day on days 3 to 10. Treatments were repeated every 28 days. Neutropenia (less than 1,500/mm3) occurred in 14 of 18 patients. Transient increases in serum glutamic-oxaloacetic transaminase levels to greater than four times baseline were noted in nine patients. Thrombocytopenia (less than 100,000 platelets/mm3) occurred in one patient. Fatigue, lethargy, and decline in performance status were marked in four of the patients. None of the patients in the low-dose interferon group and only 1 of the 15 patients in the high-dose interferon group had an objective response (7%, with a 95% confidence interval of 0 to 31%). Of the 12 patients completing at least two courses of therapy, 10 were in the high-dose group, which included the 1 objective (partial) response. This response noted at the start of the fourth course. Ten others developed progressive disease and one stopped treatment because of neurologic toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗