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Biomedical subjects

Robert Dreicer

Publications and source records attributed to Robert Dreicer.

At least 19 recordsLinked to original sources
PubMed2007

Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib.

Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic renal cell carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic renal cell carcinoma who were receiving sunitinib. Seventy-three patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring is warranted.

Adult↗
PubMed2006

Systemic chemotherapy for advanced bladder cancer: update and controversies.

Despite improvements in surgical techniques and outcomes, 5-year survival rates for patients with muscle-invasive bladder cancer remain suboptimal. Almost 50% of patients will eventually progress and develop systemic disease. Although various single agents have shown activity in patients with advanced or metastatic disease, randomized trials have demonstrated the utility of cisplatin-based combinations regimens. Despite relatively high objective response rates, the impact on survival in patients with advanced disease has been quite limited. Surgical resection in selected patients achieving significant objective response to cytotoxic therapy can contribute to long-term survival rates. The role of salvage therapy in advanced disease remains undefined. Evaluation of several active compounds has yielded unimpressive results with low objective response rates and overlapping CIs. Recognition that the maximum benefit from conventional cytotoxics has been achieved has led to the recent initiation of a number of clinical trials evaluating targeted agents in the management of advanced urothelial cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Phase II study of lenalidomide in patients with metastatic renal cell carcinoma.

BACKGROUND: Lenalidomide (LEN) is a structural and functional analogue of thalidomide that has demonstrated enhanced immunomodulatory properties and a more favorable toxicity profile. A Phase II, open-label study of LEN in patients with metastatic renal cell carcinoma (RCC) was conducted to determine its safety and clinical activity. METHODS: Patients with metastatic RCC received LEN orally at a dose of 25 mg daily for the first 21 days of a 28-day cycle. The primary endpoint was the objective response rate. Time to treatment failure, safety, and survival were secondary endpoints. RESULTS: In total, 28 patients participated in the trial and were included in the current analysis. Three of 28 patients (11%) demonstrated partial responses and continued to be progression-free for >15 months. Eleven patients (39%) had stable disease that lasted >3 months, including 8 patients who had tumor shrinkage. In total, 6 patients (21%) remained on the trial, and 5 additional patients continued to be followed for survival. The median follow-up for those 11 patients was 13.5 months (range, 8.3-17.0 months). The median survival had not been reached at the time of the current report. Serious adverse events included fatigue (11%), skin toxicity (11%), and neutropenia (36%). CONCLUSIONS: LEN demonstrated an antitumor effect in metastatic RCC, as evidenced by durable partial responses. LEN toxicities were manageable. Further studies will be required to assess the overall activity of LEN in patients with metastatic RCC.

Administration, Oral↗
PubMed2006

Southwest Oncology Group phase II study of arsenic trioxide in patients with refractory germ cell malignancies.

BACKGROUND: To the authors' knowledge, no satisfactory therapy is available for patients with refractory germ cell neoplasms. The activity and safety of arsenic trioxide in refractory germ cell tumors was assessed. METHODS: Twenty patients were treated with arsenic trioxide at a dose of 0.25 mg/kg/day and administered intravenously over 1 to 2 hours on Days 1-5 and repeated every 28 days. RESULTS: There were no complete or partial responses. The median progression-free survival was 1 month and the median overall survival was 2 months. Three patients died as a result of adverse events believed to be possibly related to treatment: ventricular arrhythmia, adult respiratory distress syndrome, and pneumonitis. CONCLUSIONS: In the current study, arsenic trioxide in the dose regimen and schedule employed was found to have no activity in men with refractory germ cell malignancies. Treatment was associated with severe toxicity. Dismal overall survival reflects the poor outcome in this patient group and highlights the acute need for new agents with activity in refractory germ cell neoplasms.

Adult↗
PubMed2006

Phase II clinical trial design: methods in translational research from the Genitourinary Committee at the Eastern Cooperative Oncology Group.

Given the increase in novel agents and difficulty with planning and completing many phase III studies, various phase II trial design options should be considered to more effectively guide phase III trial plans. The need for novel phase II trial designs has increased, given the number of novel molecular targeted therapies now available for testing, an abundance of cytostatic agents, and limited resources to conduct phase III studies for all interesting agents or combinations. This review will focus on options for phase II trial designs. We review randomized phase II designs with placebo control, randomized selection designs, and randomized discontinuation designs. As agents become available for testing in the clinic, the strengths and weaknesses of different phase II trial designs should be considered to optimize a trial development plan that guides phase III trial decisions more effectively.

Advisory Committees↗
PubMed2006

Phase I trial of thalidomide and interleukin-2 in patients with metastatic renal cell carcinoma.

BACKGROUND: The treatment of advanced renal cell cancer remains unsatisfactory, therefore new combination regimens such as thalidomide and IL-2 are of interest. A phase I trial of SC IL-2 and oral thalidomide was performed to identify the toxicity, maximum tolerated dose (MTD) and preliminary clinical activity of this regimen. METHODS: 33 patients with advanced/metastatic RCC were enrolled. An established 8-week outpatient schedule of subcutaneously administered IL-2 in escalating doses, days 1-5, for 6 weeks with a 2 week rest was utilized with daily oral thalidomide. Cohorts of 4-6 patients were treated at 4 dose levels. RESULTS: Toxicity was moderate to severe and related to dose level. All patients developed fever, chills and fatigue. 29/33 patients developed < or = Grade 2 desquamation of hands and feet and/or rash. Dose limiting toxicity (DLT) included Grade 3 neutropenia and pulmonary embolus. The maximum tolerated dose (MTD) of IL-2 and thalidomide was 9.0 MIU/m2 s.c. days 1-5, weeks 1 to 6 and 100 mg p.o. daily, respectively. A median of 2 cycles of therapy was administered (range 1-9). 2/33 patients responded (1 CR--prior IL-2 therapy, 1 PR--no prior therapy) with an overall response of 6% (95% CI, 1-20%). One minimal response was converted to a surgical CR (remains disease free at 24 + months). CONCLUSION: Outpatient administration of IL-2 and thalidomide is possible with acceptable toxicity. Further evaluation of this regimen is underway.

Adult↗
PubMed2006

Chemotherapy for advanced prostate cancer: docetaxel and beyond.

To place appropriately into context the current status of chemotherapy as a management option for patients with hormone-refractory metastatic prostate cancer, it is important to reflect on the widely held historical belief that advanced prostate cancer is a chemotherapeutic-insensitive neoplasm. This article focuses on three disease subsets: (1)metastatic, hormone-refractory, chemotherapy-naive prostate cancer;(2) metastatic, hormone-refractory, progressive prostate cancer after frontline chemotherapy; and (3) locally advanced prostate cancer. Yagoda and Petrylak evaluated the results of 26 phase II trials of antineoplastics in advanced prostate cancer published between 1987 and 1991 and found the average objective response rate was less than 10% with only a few studies having response rates in the 10% to 20%range.

Antineoplastic Agents↗
PubMed2005

Society of Urologic Oncology position statement: redefining the management of hormone-refractory prostate carcinoma.

Because patients with hormone-refractory prostate carcinoma are a very diverse group, management of these patients represents a unique challenge. Despite much research, to the authors' knowledge few studies published to date have provided definitive treatment answers. The Society of Urologic Oncology (SUO) convened a multidisciplinary panel of urologists, oncologists, and radiation oncologists to develop a treatment algorithm for patients with hormone-refractory prostate carcinoma. The resulting treatment outline was based on a review of the literature review and on the expert opinions of the panelists. The current article provided a logical progression of treatment choices that included hormonal manipulations, chemotherapeutic options, and adjunctive therapies. Future clinical trials and therapies were also discussed by the authors. Management strategies should be targeted toward the individual patient. Although significant progress has been made in understanding and treating hormone-refractory prostate carcinoma, earlier interventions would be ideal and better therapeutic approaches to prolong survival are necessary.

Algorithms↗
PubMed2005

Novel cytotoxic and biological agents for prostate cancer: where will the money be in 2005?

In 2004, docetaxel-based chemotherapy became the first treatment capable of extending life in androgen-independent prostate cancer. The era of therapeutic nihilism in this disease has thus been put to rest and a broad range of agents is being tested with the goal of improving on the successes of 2004. Lessons learned from other tumour types will need to be applied to prostate cancer in order to harness the bounty of available ideas. Target amplification or activating mutations and not merely the presence of a target are likely to be important to the success of targeted agents. Thus, the promise of the current crop of targeted agents is most likely to be realised when pursued in the context of well-credentialed targets and tested in highly translational clinical trials that are capable not only of assessing tumour response, but also of evaluating the status of the targeted pathway. The most promising agents in clinical development are reviewed.

Angiogenesis Inhibitors↗
PubMed2005

Adjuvant and neoadjuvant chemotherapy for bladder cancer: management and controversies.

Radical cystectomy remains the gold standard treatment for muscle-invasive bladder cancer. Although surgery achieves excellent local control, within 5 years almost 50% of patients relapse and subsequently progress to develop systemic disease. Transitional cell carcinoma of the bladder is sensitive to chemotherapy. Although platinum-based chemotherapy can produce relatively high overall response rates, the impact on the survival of patients with advanced disease has, at best, been limited. Randomized trials of cisplatin-based chemotherapy regimens in the neoadjuvant setting have demonstrated the potential to improve survival. By comparison, adjuvant studies have been plagued by suboptimal trial design, limited patient numbers, and lack of standardization of the chemotherapy regimens used. With the introduction of new cytotoxic drugs and novel small molecules, there is a need for well-designed studies to address the optimal utility of perioperative therapy in high-risk patients with bladder cancer.

Chemotherapy, Adjuvant↗
PubMed2004

Phase III trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium.

BACKGROUND: The regimens of carboplatin plus paclitaxel (CP) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) were compared in patients with advanced urothelial carcinoma. METHODS: Patients with metastatic urothelial carcinoma were randomized to receive either CP (paclitaxel at a dose of 225 mg/m(2) and carboplatin [targeted area under the concentration-time curve (AUC) of 6] given every 21 days) or the standard M-VAC dosage. RESULTS: Eighty-five patients were randomized to the respective treatment regimens (41 to CP and 44 to M-VAC). Response rates and overall survival were similar for both treatment arms. Patients treated with CP had an overall response rate of 28.2% (95% binomial confidence interval, 15.0-44.9%) compared with an overall response rate of 35.9% for the M-VAC arm (95% binomial confidence interval, 21.2-52.8%) (P = 0.63, Fisher exact test). The median progression-free survival among patients who were treated with M-VAC was 8.7 months and was 5.2 months for patients receiving CP (P = 0.24, log-rank test). At a median follow-up of 32.5 months, the median survival for patients treated with M-VAC was 15.4 months versus 13.8 months for patients treated with CP (P = 0.65, log-rank test). Patients treated with M-VAC were found to have more severe worst-degree toxicities compared with patients treated with CP (P = 0.0001). There were no significant differences with regard to quality of life as assessed by the Functional Assessment of Cancer Therapy-Bladder (FACT-BL) instrument (P = 0.33). CONCLUSIONS: Interpretation of the results of this study must be made with caution because the study failed to reach its accrual goal. Patients treated with CP had a median survival of 13.8 months compared with 15.4 months for patients treated with M-VAC. Patients treated with CP appeared in general to better tolerate their treatment; however, there were no significant differences noted with regard to measured quality of life parameters.

Aged↗
PubMed2004

Appetite and cancer-associated anorexia: a review.

Appetite is governed by peripheral hormones and central neurotransmitters that act on the arcuate nucleus of the hypothalamus and nucleus tactus solitarius of the brainstem. Cancer anorexia appears to be the result of an imbalance between neuropeptide-Y and pro-opiomelanocortin signals favoring pro-opiomelanocortin. Many of the appetite stimulants redress this imbalance. Most of our understanding of appetite neurophysiology and tumor-associated anorexia is derived from animals and has not been verified in humans. There have been few clinical trials and very little translational research on anorexia despite its prevalence in cancer.

Animals↗
PubMed2004

Phase II trial of neoadjuvant docetaxel before radical prostatectomy for locally advanced prostate cancer.

OBJECTIVES: To perform a Phase II trial of docetaxel administered on a weekly schedule for 6 weeks before radical prostatectomy (RP) in patients with locally advanced prostate cancer. METHODS: Treatment consisted of six doses of docetaxel 40 mg/m(2) intravenously administered weekly for 6 weeks followed by RP. Eligibility criteria included clinical Stage T2b, prostate-specific antigen (PSA) level 15 ng/mL or greater or Gleason sum 8 or greater, and no evidence of metastatic disease. The primary endpoint was feasibility and drug-related and surgical-related toxicities. Secondary endpoints included pre-RP PSA level, local response, pathologic outcomes, and time to PSA failure. RESULTS: Twenty-nine patients were entered; 80% completed all 6 weeks of therapy and 97% underwent RP. The median PSA level was 12 ng/mL (range 2.5 to 43.3), the median Gleason sum was 8 (range 6 to 9), and all had Stage T2b or greater disease. A statistically significant reduction in the prechemotherapy versus postchemotherapy mean PSA level was observed (12.00 +/- 1.86 ng/mL versus 8.42 +/- 1.63 ng/mL, P <0.03), with 79% of patients experiencing some reduction and 24% a more than 50% reduction in PSA level in response to docetaxel alone. No unexpected toxicities and no intraoperative complications occurred. Pathologic analysis demonstrated residual carcinoma in all cases. Three patients (11%) had organ-confined disease, and 26 (93%) had achieved an undetectable PSA postoperatively. At a median follow-up of 23 months (range 1.5 to 36), 20 patients were disease free with no additional therapy. CONCLUSIONS: This trial establishes the baseline effect of short-course high-dose docetaxel alone on locally advanced prostate cancer. Additional study of this paradigm with other agents alone and in combination with docetaxel seems warranted.

Aged↗
PubMed2003

Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium: a trial of the Eastern Cooperative Oncology Group.

BACKGROUND: Gemcitabine and docetaxel are active agents in advanced urothelial carcinoma. A Phase II trial of this combination was performed to determine the activity and toxicity of these agents in a multiinstitutional setting in patients previously treated with one prior chemotherapy regimen. METHODS: Twenty-nine eligible patients with advanced urothelial carcinoma were treated with docetaxel at a dose of 40 mg/m(2) over 1 hour followed by gemcitabine, 800 mg/m(2), over 30 minutes, both intravenously (i.v.) on Days 1 and 8. Cycles were repeated every 21 days until disease progression or a maximum of 6 cycles. RESULTS: Five patients obtained an objective response for an overall response rate of 17% (90% confidence interval, 7-33%). One patient achieved a complete clinical response. The median overall survival of the group was 7.7 months. Toxicity was moderate with granulocytopenia, anorexia, and fatigue being the most commonly noted side effects. CONCLUSIONS: Gemcitabine and docetaxel is an active second-line combination in patients with advanced urothelial carcinoma. Responses in visceral, lymph node, and soft tissues sites were observed. Granulocytopenia without fever, fatigue, and anorexia was common. Thromboembolic symptoms were reported and are of concern. The combination of gemcitabine and docetaxel has the potential to palliate a subset of previously treated patients with an adequate performance status.

Aged↗
PubMed2003

Overview of advanced urothelial cancer trials of the Eastern Cooperative Oncology Group.

Advanced transitional cell carcinoma of the urothelium is an aggressive malignancy characterized by a median survival period of less than 1 year. Although this disease is moderately chemotherapy-sensitive, to the authors' knowledge the impact of therapy reported to date on survival has been minimal. The authors presented an overview of the results from a series of clinical trials conducted over a 25-year period under the auspices of the Eastern Cooperative Oncology Group. They reviewed a series of antineoplastic agents identified by these studies with activity in advanced urothelial cancer and discussed current and future investigational goals and directions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Paracolic recurrence of stage I seminoma.

Paracolic recurrence of testicular germ cell tumors is rare and is usually related to incomplete excision of the ipsilateral spermatic cord. We describe a paracolic recurrence outside of the standard radiation field of a low-stage pure seminoma that was managed by chemotherapy and surgical excision, rendering the patient disease free with short-term follow-up.

Adult↗
PubMed2003

A phase II study of 13-cis retinoic acid plus interferon alpha-2a in advanced stage penile carcinoma: an Eastern Cooperative Oncology Group study (E3893).

PURPOSE: Combined biological therapy with 13-cis-retinoic acid (13-cRA) and interferon alpha-2a (IFN alpha-2a) was reported to be highly effective in squamous cell carcinoma of the cervix and skin. Squamous cell carcinoma of the penis is rare in the United States, accounting for less than 1/2% of all male malignancies. Because of the association of infection with human papillomavirus with both carcinomas of the cervix and penis and their shared squamous cell histology, we carried out a phase II study of 13-cRA and IFN alpha-2a in carcinoma of the penis. MATERIALS AND METHODS: Eighteen ambulatory patients with surgically unresectable, recurrent, and/or metastatic squamous cell carcinoma of the penis were treated with IFN alpha-2a, 3MU/day administered subcutaneously and 13-cRA, 1 mg/kg orally daily for at least eight weeks, unless intolerable toxicity occurred. RESULTS: One patient was ineligible; one patient withdrew prior to treatment. Among the 16 eligible, treated patients, there was one complete response. Fourteen patients had progressive disease as their only treatment effect. Two patients were unevaluable for tumor response because they had no follow-up tumor measurements. No unexpected treatment-related toxicities were found on study. The only common form of grade 3 toxicity was hypertriglyceridemia found in eight of the 17 patients (47%). No toxicities above grade 3 were observed. CONCLUSION: In contrast to its benefit in squamous cell carcinomas of the cervix and skin, the combination of 13-cRA and IFN alpha-2a has low efficacy in advanced carcinoma of the penis.

Adult↗