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Biomedical subjects

E D Crawford

Publications and source records attributed to E D Crawford.

At least 19 recordsLinked to original sources
PubMed1992

Controversies in the treatment of metastatic prostate cancer.

BACKGROUND: Prostate cancer is the most common cancer in American men today. Unfortunately, at the time of diagnosis, most men will have either regional or distant metastatic disease. METHODS: Six hundred three patients with advanced prostate cancer who could be examined were randomized in a double-blind, placebo-controlled trial to receive the luteinizing hormone-releasing hormone (LHRH) agonist leuprolide with either flutamide or placebo. RESULTS: Patients receiving the combined therapy arm of leuprolide and flutamide had an increased progression-free survival time of 16.9 versus 13.8 months and a survival advantage of 35.1 versus 20.3 months. A more striking difference was found in the subset of patients receiving combination therapy who had good performance and minimal disease. CONCLUSIONS: There appears to be a definite advantage of combination therapy over leuprolide alone, especially in patients with minimal disease and good performance. Another larger intergroup study using orchiectomy and flutamide versus orchiectomy and placebo is currently underway.

Double-Blind Method↗
PubMed1992

Treatment with gallium nitrate: evidence for interference with iron metabolism in vivo.

Gallium, when bound to transferrin, has been previously shown to cause tumor cell cytotoxicity by preventing cellular uptake of transferrin bound iron in vitro. Patients treated with constant infusion gallium nitrate for carcinoma show a rise in serum iron within 6 hr of the start of treatment. Serum iron returns to baseline by 24 hr post-infusion. Atomic analysis of iron and gallium content of Sephadex G-150 fractions of treatment sera indicate that about an equimolar amount of gallium and iron are associated with transferrin. These gallium and iron concentrations result in inhibition of transferrin mediated iron uptake in vitro, and in vivo allow for > 90% saturation of transferrin with metal. All seven patients who completed two courses of gallium therapy exhibited hypochromic microcytic anemia (mean fall in hemoglobin 3.5 grams %). Evidence for red cell iron depletion was confirmed by an increase (mean 3.3-fold) in zinc protoporphyrin levels. Since transferrin receptor increases on gallium treated iron requiring cells in vitro, we assessed cell surface transferrin receptor on peripheral blood lymphocytes by measuring fluorescent transferrin receptor antibody binding. A population of highly transferrin receptor positive cells peaks at 48 hr into the infusion. DNA analysis as well as double staining indicate the majority of transferrin receptor positive cells are unstimulated B lymphocytes. These studies provide the first documentation that constant infusion gallium treatment results in significant interference with iron metabolism and evidence for tissue iron depletion in vivo. These changes may correlate with therapeutic effects of gallium such as tumor response.

Animals↗
PubMed1992

Chemoprevention of prostate cancer: guidelines for possible intervention strategies.

The "natural history" of prostate cancer may bedevil the development of guidelines for chemoprevention interventions. Can strategies be designed to direct agents to those lesions which have the potential to develop localized extension that may become symptomatic or metastatic disease? Of necessity our interventions will focus on the identification and quantification of appropriate biomarkers as intermediate endpoints, although no reliable endpoints for prostate cancer have yet been identified. The reduction of prostate cancer incidence may be the ultimate objective, but a decrease in the progression of microfocal or "latent" cancer may well be just as effective as prevention when the age of the target population and competing causes of death are taken into account. Early intervention strategies must focus on the analysis of the interactions of the chosen chemopreventive agents upon precancerous and cancerous cellular dynamics in the prostate. Whether the requirements of such molecular epidemiology necessitate a more deliberate strategy of Phase II studies or a high risk-high gain strategy of a broad Phase III study is open to debate. Factorial designs for proposed randomized chemoprevention trials may be desirable to test multiple chemopreventive agents simultaneously, provided knowledge of the biochemical synergism of the agents is solid. Stratification of study participants by degree of risk will ameliorate concerns regarding the precision targeting of lesions at different stages in the precancer/cancer continuum.

Androstenes↗
PubMed1992

Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma.

The unavailability of effective treatment of metastatic hormone refractory prostatic carcinoma warrants trials of new and promising treatments. Coumarin is an investigational new drug that has produced objective tumor regression in some patients with metastatic renal cell carcinoma and malignant melanoma. Coumarin has shown activity against prostatic carcinoma in the Dunning R-3327 rat prostatic adenocarcinoma model. Forty-eight patients with metastatic hormone naive (5 stage D1 and 10 stage D2) or hormone refractory (33 stage D3) prostatic carcinoma of average age 67.6 years (range 46-86) and ECOG performance status of 2 or better were given 3 grams coumarin daily by mouth and evaluated monthly for toxicity and response by rigid criteria in a multicenter trial. Toxicity was limited to asymptomatic SGOT elevations in 3 patients and nausea and vomiting in 4 patients that required cessation of therapy in 2. Eligibility and protocol violations removed 6 additional patients from response evaluation. There were no complete responses. Partial responses (3 of 40 patients, 8%) occurred in 2 patients with bidimentionally measurable disease and 1 patient with disease evaluable by bone scan and elevated prostate specific antigen and prostatic acid phosphatase. The remaining patients progressed after 1 to 12 (average 4.4) months. Coumarin is a relatively nontoxic drug that may warrant further trials in a subset of patients with prostatic carcinoma.

Adult↗
PubMed1992

Phase II evaluation of piroxantrone in renal cell carcinoma. A Southwest Oncology Group Study.

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of piroxantrone (150 mg/m2 q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 32 eligible patients, there were no partial nor complete responses. There were two mixed responses. Significant white cell toxicity, anemia, nausea, and vomiting were observed. Mild or moderate degrees of fever, malaise, and stomatitis occurred. No significant cardiac toxicity was noted. Piroxantrone does not have significant activity as a single agent in advanced renal cell carcinoma.

Adult↗
PubMed1992

Phase II evaluation of didemnin B in advanced adenocarcinoma of the kidney. A Southwest Oncology Group study.

The Southwest Oncology Group studied the response rate and toxicity of didemnin B (3.47 mg/m2 i.v. q 28 days) in patients with advanced renal cell carcinoma. There were no responses in 22 response evaluable patients. Toxicity was significant with 10 patients having grade 3 or 4 toxicity. Toxicity seen included nausea and vomiting, exacerbation of coronary artery disease, hyperglycemia, anorexia, diarrhea and hepatitis. Didemnin B was toxic but inactive in patients with renal cell treated at this dose.

Adenocarcinoma↗
PubMed1992

Treatment of stages B3 and C seminoma with chemotherapy followed by irradiation therapy. Southwest Oncology Group Study.

Beginning in 1981, 28 patients with advanced seminoma were treated with combination chemotherapy followed by irradiation to evaluate the possibility of improved survival using both modalities. The treatment protocol consisted of two courses of vincristine, actinomycin-D, and cyclophosphamide followed by reassessment. Those initially presenting with Stage B3 disease who achieved a complete response to two cycles of chemotherapy then underwent irradiation. All others were given a third course of chemotherapy before undergoing irradiation. The pre-radiation portion of this protocol produced a complete response rate of only 25 percent, substantially less than other, more recent, protocols. Radiation therapy produced a complete response in 69 percent of those who did not achieve a complete response from chemotherapy, increasing the complete response rate from 25 percent to 64 percent. Given this response rate to radiation therapy and the difficulty of dissection and associated morbidity with the surgical excision of postchemotherapy residual masses, the best option at this time may be observation with salvage chemotherapy and/or radiation reserved for those with disease progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Combination cisplatin and dichloromethotrexate in patients with advanced bladder cancer. Phase 2. A Southwest Oncology Group study.

The combination of cisplatin and dichloromethotrexate is a pharmacologically rational strategy designed to avoid the nephrotoxicity associated with the systemic chemotherapy of bladder cancer. Of 97 patients with metastatic bladder cancer entered into this study 73 with good renal function received cisplatin and dichloromethotrexate, while 24 with impaired renal function received dichloromethotrexate alone. No responses were noted in the latter group. A 42% response rate (95% exact confidence interval 30.0 to 55.2%), including 9 patients (14%) who achieved a complete response, was observed in the combination group. The toxicity patterns in both groups of patients were consistent with the hypothesis that renal toxicity would be ameliorated with the use of the methotrexate analogue. However, the failure to achieve a higher overall response rate despite near maximum tolerated doses of dichloromethotrexate discourages future studies with this agent. New agents for metastatic bladder cancer should be tested as first line therapy.

Adult↗
PubMed1992

Phase 1 trial of oral bropirimine in superficial bladder cancer.

A total of 34 patients with measurable superficial transitional cell cancer of the bladder entered into a phase 1, nonrandomized, noncomparative trial to assess the toxicity of the oral interferon inducer bropirimine. Of the patients 26 were also evaluable for response. The toxicity of bropirimine was minimal. At the 3-month evaluation 6 patients had experienced complete regression of tumor and had negative cytology studies, and 2 had partial responses. The majority of complete responses were in patients with carcinoma in situ only, with most responses seen at higher dose levels. One patient with papillary tumor and carcinoma in situ had a complete response. Some early responses appear to be durable. Most importantly, a high rate of complete response was noted at higher dose levels among patients who had failed prior therapy with bacillus Calmette-Guerin. Further clinical trials of bropirimine in bladder cancer appear warranted.

Administration, Oral↗
PubMed1992

Prevention of urinary tract infection and bacteremia following transurethral surgery: oral lomefloxacin compared to parenteral cefotaxime.

A multicenter, randomized, open label study compared the safety and efficacy of a single dose of oral lomefloxacin, a broad-spectrum antimicrobial agent of the quinolone class, to a single parenteral dose of cefotaxime, a third generation cephalosporin, for prophylaxis in transurethral surgery. Of the 230 patients initially recruited 182 were considered evaluable: 92 in the lomefloxacin group and 90 in the cefotaxime group. Both study groups were well balanced with respect to demographics and transurethral procedures. Efficacy and safety were evaluated with urine cultures, clinical laboratory evaluations and monitoring of adverse events. The success rate among the lomefloxacin patients was 98% versus 94% in the cefotaxime patients. The difference was not statistically significant. Adverse events, regardless of attributability, were reported by 16% of the lomefloxacin patients and 17% of the cefotaxime patients, respectively. Our results indicate efficacy and safety profiles of lomefloxacin equivalent to cefotaxime. Lomefloxacin has the economic advantage of an oral route of administration compared to the parenteral route of cefotaxime for prophylaxis in transurethral genitourinary procedures.

Administration, Oral↗
PubMed1992

Phase II study of platinum and mitoxantrone in metastatic prostate cancer: a Southwest Oncology Group Study.

44 eligible patients with measurable or evaluable metastatic prostate cancer were treated with monthly cycles of cisplatin and mitoxantrone. Good-risk patients received cisplatin 60 mg/m2 intravenously and mitoxantrone 10 mg/m2 intravenously every 4 weeks. The dose in poor-risk patients (elderly or white blood cell count less than 4000/microliters, 4 x 10(9)/l, or extensive prior radiation) was reduced to 8 mg/m2. Toxicity was manageable and consisted primarily of myelosuppression. There were no complete responses and the partial response rate was only 12%. Median progression-free survival was 2.7 months for measurable and 4.1 months for evaluable disease patients. Median survivals were 4.9 and 8.7 months, respectively. This combination has minimal activity in hormone refractory metastatic prostate cancer.

Adenocarcinoma↗
PubMed1992

Challenges in the management of prostate cancer.

An estimated 32,000 American men will die of prostate cancer this year. Local prostate cancer may be successfully treated by radical prostatectomy or radiotherapy. Advanced cases may necessitate the use of hormonal ablation with bilateral orchiectomy, an approach that is regarded as the gold standard of therapy but not always the preferred treatment of patients. Oestrogen therapy is an alternative but is associated with side effects, such as hot flushes and gynaecomastia, which frequently lead to treatment cessation. Luteinising hormone-releasing hormone (LHRH) analogues work by initially producing a surge of androgen, followed by a down-regulation in hormone production to effect a medical castration. Various groups have studied the effects of androgen blockade administered as monotherapy and as combination therapy (LHRH analogue plus antiandrogen). The National Cancer Institute intergroup protocol 0036, which is the largest cooperative study to date of patients with advanced prostatic cancer, showed that combination therapy with leuprolide and flutamide offered greater benefit in both time to disease progression and median survival while circumventing tumour flare and its associated symptoms. Thus, combination therapy for total androgen ablation may become the new treatment standard for advanced prostatic cancer, pending further studies in the efficacy and cost-effectiveness of all available treatments.

Black People↗
PubMed1992

A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

PURPOSE: A prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. RESULTS: As expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Response rates were superior for the M-VAC regimen compared with single-agent cisplatin (39% v 12%; P less than .0001). Similarly, the progression-free survival (10.0 v 4.3 months) and overall survival (12.5 v 8.2 months) were significantly greater for the combined therapy arm. CONCLUSION: Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.

Adult↗
PubMed1992

Etoposide in the treatment of hormone-refractory advanced carcinoma of the prostate.

The leading cause of cancer in males in the United States, prostate cancer accounts for 22% of all new cancers, with 132,000 new cases projected to be diagnosed in 1992. While localized prostate cancer can be cured, up to two thirds of patients present with advanced disease. Androgen deprivation remains the mainstay of treatment for advanced prostate carcinoma. Recurrent disease, however, is invariably refractory to further hormone manipulations. The development of hormone-resistant tumor cells may be explained either by a multi-clones theory, by mutation of previously sensitive tumor cell clones, or, most likely, by both mechanisms. Thus, vigorous efforts are needed to develop nonendocrine treatment approaches. Such efforts have been complicated by the difficulty of assessing therapeutic response in patients with prostate cancer, because the typical metastatic bone lesions seen in these patients are difficult to measure accurately and patients seldom have disease in the lung, lymph nodes, or soft tissue. A variety of single chemotherapeutic agents have been tested against recurrent disease, with widely divergent response rates achieved. Trials of chemohormonal therapy have likewise proved disappointing to date. Preliminary results from an ongoing trial of oral etoposide in patients with recurrent prostate cancer are discussed.

Administration, Oral↗
PubMed1992

Management of regional lymphatic drainage in carcinoma of the penis.

Radical ilioinguinal lymphadenectomy remains the mainstay of treatment for certain genitourinary carcinomas either with the propensity for or with clinical evidence of metastases to the inguinal-pelvic region. The most frequent indication for this procedure in urologic practice is carcinoma of the penis, followed by carcinoma of the urethra, scrotum, and testis with scrotal invasion. This article reviews the anatomy of the inguinal and iliac region and presents a detailed discussion of the surgical technique and its most recent modifications.

Humans↗
PubMed1992

Complications of intravesical chemotherapy.

A variety of intravesical chemotherapeutic agents are now available for the treatment of superficial transitional-cell carcinoma of the bladder. The toxicities associated with these agents may make one more appealing than another in the face of similar efficacies. Intravesical instillations of thiotepa have resulted in incidences of leukopenia of 8% to 54%, of thrombocytopenia of 3% to 31%, and of irritative voiding symptoms of 12% to 69%. Close monitoring of blood counts prior to weekly instillations remains vital in preventing myelosuppressive complications. The complications associated with the intravesical use of mitomycin C are mainly chemical cystitis and contact dermatitis. Additionally, allergic reactions have been documented. Most of these complications respond to cessation of therapy with application of topical steroids as needed. Complications of reduced bladder capacity, bladder-wall calcifications, and myelosuppression are uncommon. Toxicities associated with the use of doxorubicin, epirubicin, and ethoglucid are almost exclusively local and usually described as mild to moderate dysuria, frequency, or urgency. Case reports of systemic reactions to doxorubicin are notable in that the patients responded well to diphenhydramine and, in one severe case, epinephrine. Other adverse effects such as reduced bladder capacity, fever, and nausea and vomiting are very uncommon. New agents, such as mitoxantrone, are undergoing phase I and phase II studies. The ideal agent, which would be highly effective and minimally toxic, remains to be developed.

Administration, Intravesical↗