Biomedical subjects

R Dreicer

Publications and source records attributed to R Dreicer.

At least 19 recordsLinked to original sources

PubMed2006

Phase I trial of three-weekly docetaxel, carboplatin and oral lenalidomide (Revlimid) in patients with advanced solid tumors.

INTRODUCTION: Lenalidomide is an immunomodulatory derivative of thalidomide with significantly greater in vitro activity and a different toxicity profile. In preclinical trials it has shown synergy with chemotherapy. PATIENTS AND METHODS: Primary objective of this study was to determine the maximum tolerated doses of docetaxel and carboplatin when combined with oral lenalidomide in a standard phase I study design. Between September 2004 and May 2005, 14 patients with pathologically proven solid tumors, < or =2 prior chemotherapy regimens, performance status ECOG 0/1, and adequate organ function were enrolled. Dose limiting toxicities (DLT) were defined as > or = grade 3 non-hematological, or grade 4 hematological toxicity. No growth factors were used during cycle 1. RESULTS: Three of four patients treated at dose level 1, docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, and lenalidomide 10 mg orally daily on Days 1-14 of a 21 day cycle experienced DLT (grade 3 electrolyte changes in two patients, and grade 4 neutropenia in one patient). Ten patients were treated at dose level -1, docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, and lenalidomide 5 mg orally daily on Days 1-14 of a 21 day cycle with one DLT (Grade 4 neutropenia). There were no treatment-related deaths or irreversible toxicities. Of the 14 response-evaluable patients, five achieved a partial response (5 out of 9 patients with non-small cell lung cancer. CONCLUSIONS: Docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, with lenalidomide 5 mg orally daily on Days 1-14 days of a 21 day cycle is the maximum tolerated dose without the use of prophylactic growth factors. This combination is active and further evaluation in a phase II trial is warranted.

Administration, Oral↗

PubMed2001

Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases.

BACKGROUND: This study evaluated the dose-response relation for zoledronic acid, a new generation high potency bisphosphonate, given as a 5-minute infusion in patients with malignant osteolytic disease. METHODS: Two-hundred eighty patients with osteolytic lesions due to metastatic breast carcinoma or multiple myeloma were randomized to double-blind treatment with either 0.4, 2.0, or 4.0 mg of zoledronic acid or 90 mg pamidronate. The primary efficacy endpoint was the proportion of patients receiving radiation to bone. Other skeletal-related events, bone mineral density (BMD), bone markers, Eastern Cooperative Oncology Group performance status, pain and analgesic scores, and safety also were evaluated. RESULTS: Zoledronic acid at doses of 2.0 and 4.0 mg and pamidronate at a dose of 90 mg each significantly reduced the need for radiation therapy to bone (P < 0.05) in contrast with 0.4 mg zoledronic acid, which did not. Skeletal-related events of any kind, pathologic fractures, and hypercalcemia also occurred less frequently in patients treated with 2.0 or 4.0 mg zoledronic acid or pamidronate than with 0.4 mg zoledronic acid. Increases in lumbar spine BMD (6.2-9.6%) and decreases in the bone resorption marker N-telopeptide (range, -37.1 to -60.8%) were observed for all treatment groups. Skeletal pain, fatigue, nausea, vomiting, and headache were the most commonly reported adverse events. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate. CONCLUSIONS: A 5-minute infusion of 2.0-4.0 mg zoledronic acid was at least as effective as a 2-hour 90-mg pamidronate infusion in treatment of osteolytic metastases. A 0.4-mg dose of zoledronic acid was significantly less effective. Both zoledronic acid and pamidronate were well tolerated.

Antineoplastic Agents↗

PubMed2001

Locally advanced prostate cancer.

Standard therapy for clinically localized prostate cancer includes radical prostatectomy, external beam radiotherapy, or transperineal interstitial brachytherapy. Patients eligible for standard therapy are those with low risk features as defined by various risk group classifications, which generally include clinical stage T1 or T2a, serum prostate-specific antigen (PSA) less than 10 ng/mL, and biopsy Gleason sum of 6 or less. Although there has been important evolution in the performance of these techniques, particularly with respect to functional outcomes, these approaches for low-risk disease are relatively mature, and the cure rates with each of these therapies are similar in this patient population; locally advanced disease is more difficult to cure, however. Biochemical disease-free survival rates in men undergoing radical prostatectomy are clearly related to the pathologic stage. Prognostic groups can be defined based on pathologic stage with increasingly worse outcomes based on extracapsular extension (ECE), margin status, and the status of the lymph nodes and seminal vesicles. In patients with low risk features, the positive margin rate is generally low, making the presence or absence of ECE the dominant variable in predicting the likelihood of treatment failure. These observations suggest that more aggressive therapy is needed to cure those who are likely to have ECE or other adverse histologic features. Several nomograms predicting the likelihood of ECE or 5-year biochemical failure rates are now in routine clinical use, and can be used to select men at high risk of failure with single modality therapy for more aggressive treatment strategies. However, the optimal form of aggressive therapy for these patients is unknown.

Adenocarcinoma↗

PubMed2001

Locally advanced and metastatic bladder cancer.

Metastatic transitional cell carcinoma of the bladder is an aggressive neoplasm characterized by rapid growth and dissemination with a median survival of typically less than 1 year. Despite the availability of a myriad of antineoplastics with moderate-significant anti-tumor activity yielding overall response rates in the 40% to 80% range, randomized trials continue to demonstrate median survival rates in the 13- to14-month range, with very limited long-term survival. Subsets of patients with advanced bladder cancer present additional management problems, including those with renal insufficiency or nontransitional-cell histology. Various observers have noted the similarity in treatment outcomes in advanced bladder cancer and extensive small cell lung cancer where chemotherapy produces relatively high response rates but with limited impact on survival. The optimal chemotherapy combination for patients with advanced bladder cancer remains undefined, however, there is increasing recognition that in order to achieve tangible improvements in complete response rates and survival in this disease will likely require a combination of chemotherapy and targeted molecular therapies and in some settings adjunctive surgery.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Phase II trial of neoadjuvant estramustine and etoposide plus radical prostatectomy for locally advanced prostate cancer.

OBJECTIVES: To report the results of a Phase II trial of neoadjuvant estramustine and etoposide before radical prostatectomy in patients with locally advanced disease. METHODS: Treatment consisted of three cycles of estramustine (10 mg/kg/day) and etoposide (50 mg/m(2)/day) orally on days 1 through 21, repeated every 28 days, followed by radical prostatectomy. The eligibility criteria included locally advanced prostate cancer (clinical Stage T2b/c or T3, prostate-specific antigen [PSA] level of 15 ng/mL or greater, or Gleason score of 8 or higher) without evidence of metastatic disease. The median PSA level was 14 ng/mL (range 5.3 to 50), the median Gleason score was 7 (range 6 to 9), and 44% had Stage T2b/c or T3 disease. The primary endpoint was feasibility of neoadjuvant therapy and radical prostatectomy, including drug and surgery-related toxicities. Secondary endpoints included the pre-prostatectomy PSA level, local response, pathologic outcomes, and time to PSA failure. RESULTS: Eighteen patients were entered and completed all three cycles of therapy, and 16 (89%) underwent radical prostatectomy. A local response occurred in 15 (94%) of 16 patients with palpable tumors, and the serum PSA reached undetectable levels after therapy and before radical prostatectomy in 9 patients (50%). Five patients (28%) experienced grade 3 toxicity (two with deep venous thrombosis, two with neutropenia, and one with diarrhea) and one (6%) experienced grade 4 toxicity (pulmonary embolus) before surgery. The median operative time was 125 minutes, the mean blood loss was 665 mL, and the mean length of stay was 2.5 nights. Five minor surgical complications occurred in 4 patients. The pathologic analysis demonstrated residual carcinoma with squamous metaplasia and androgen deprivation effect in all patients. Five patients (31%) had organ-confined disease and 9 patients (56%) had specimen-confined disease. All patients achieved an undetectable PSA level postoperatively and at a median follow-up of 14 months (range 5 to 20) and without additional therapy, all 14 patients with negative lymph nodes were disease free. CONCLUSIONS: This trial confirms the feasibility of radical prostatectomy with acceptable surgical morbidity after neoadjuvant therapy with estramustine and etoposide in patients with locally advanced prostate cancer. However, this regimen is associated with estramustine-induced thromboembolic toxicity. The results of the pathologic analysis suggest a higher than expected rate of organ-confined and specimen-confined disease, but little histologic evidence of antitumor effect beyond that associated with androgen deprivation. Additional study of this paradigm with other drug regimens is warranted.

Antineoplastic Agents, Hormonal↗

PubMed2001

Preliminary observations of single-agent docetaxel as neoadjuvant therapy for locally advanced prostate cancer.

Patients with locally advanced prostate cancer present a significant therapeutic dilemma. Despite aggressive local therapies, including radical prostatectomy (RP), these patients are at high risk for biochemical failure. Several research groups have recently demonstrated the feasibility of hormonal and chemohormonal therapy before RP, but limited published data are available regarding the usefulness of chemotherapy without hormonal therapy in the neoadjuvant setting. At Cleveland Clinic Foundation, a phase II trial was initiated to evaluate a 6-week course of docetaxel, 40 mg/m(2) intravenously every 7 days, followed by RP in patients with locally advanced prostate cancer. RP was to be performed within 3 weeks of completion of neoadjuvant chemotherapy. The primary endpoint of this study is pathologic complete response. Preliminary toxicity data suggest that weekly docetaxel is well tolerated and does not increase the risk of perioperative or post operative complications. Reductions in prostate-specific antigen levels were noted in seven of 10 patients who completed the 6-week course of neoadjuvant docetaxel. The neoadjuvant use of investigational cancer therapies may allow for relatively rapid assessment of their antitumor activity.

Aged↗

PubMed2001

Phase II trial of GM-CSF in advanced prostate cancer.

OBJECTIVES: Prostate-specific antigen only disease progression following definitive therapy is significant therapeutic dilemma. The benefit of hormonal therapy remains unproven and is associated with significant toxicity, more pronounced with chronic use. Biochemical progression following hormonal therapy has no standard treatment. New approaches to the management of this subset of patients are needed. A previous study in advanced prostate cancer demonstrated biologic activity of granulocyte macrophage-colony stimulating factor. The purpose of this study was to evaluate the activity of granulocyte macrophage-colony stimulating factor in a less heavily pretreated population. MATERIALS AND METHODS: Sixteen patients with advanced prostate cancer, 7 hormonally naïve, and 9 androgen independent, were treated with granulocyte macrophage-colony stimulating factor administered subcutaneously at 250 microg three times a week for up to 6 months. Prostate-specific antigen measurements were obtained every 2 weeks. RESULTS: No patient achieved an objective response. Six patients demonstrated a 10-15% decline in their baseline prostate-specific antigen which was maintained during the entire treatment period. Five of these 6 patients demonstrated a rise in their prostate-specific antigen following study completion. Therapy was well tolerated, with only 1 grade 3 event which was not treatment-related. CONCLUSIONS: Granulocyte macrophage-colony stimulating factor demonstrates modest biologic evidence of activity in prostate cancer as manifested by prostate-specific antigen response. Further investigation of the mechanism of activity and additional clinical evaluation of this agent seems warranted.

Adenocarcinoma↗

PubMed2001

Neoadjuvant chemotherapy in the management of muscle-invasive bladder cancer.

Muscle-invasive bladder cancer is typically an aggressive solid tumor with the propensity for early systemic dissemination. Although radical cystectomy remains the gold standard intervention, the high rate of systemic failure has prompted investigators to evaluate various strategies to attempt to improve survival, including the early administration of systemic chemotherapy. These efforts have provided mixed results with two recently completed trials providing conflicting results. Other strategies include attempts to both preserve the bladder using combinations of limited surgical resection, systemic chemotherapy, and radiotherapy. This review focuses on the potential of neoadjuvantly administered therapies to impact the management of muscle-invasive bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Second-generation interferons for cancer: clinical targets.

IFNs were the first new therapeutic products resulting from recombinant DNA technology. IFNs were also the first human proteins effective in cancer treatment. There is however much to be discovered which will lead to new clinical applications. Areas which represent major research challenges for full understanding and application of the IFN system are: (i) the diversity of the IFN family; (ii) the role of induction; (iii) molecular mechanism of action; (iv) cellular modulatory effects; (v) advantages of combinations, and (vi) identification of new therapeutic indications. This review will emphasize the diversity of the IFN family and chemical modifications which will result in second-generation IFNs. Pre-clinical and clinical findings form the basis for new therapeutic directions in chronic myelogenous leukemia, lymphomas, myelomas, melanoma, urologic malignancies, primary brain tumors, and ovarian carcinoma.

Animals↗

PubMed2000

Phase II study of cisplatin and paclitaxel in advanced carcinoma of the urothelium: an Eastern Cooperative Oncology Group Study.

PURPOSE: Cisplatin and paclitaxel are active agents in advanced urothelial cancer. A phase II trial of this combination was performed to determine the activity and toxicity of these agents in a multi-institutional setting. PATIENTS AND METHODS: Fifty-two patients with advanced urothelial carcinoma were treated on one day with paclitaxel 175 mg/m(2) over 3 hours followed by cisplatin 75 mg/m(2), both intravenously, every 21 days. Cycles were repeated every 21 days until progression or a maximum of six cycles. RESULTS: Twenty-six patients obtained an objective response, for an overall response rate of 50% (95% confidence interval, 36% to 64%). Four patients achieved complete clinical responses. The median overall survival time for the group was 10.6 months. Toxicity was moderate, with granulocytopenia and neurotoxicity being the most common side effects noted. CONCLUSION: The combination of cisplatin and paclitaxel is active in advanced urothelial cancer. Responses in visceral, nodal, and soft tissues sites were observed. Granulocytopenia without fever and grade 2/3 neurotoxicity were common. The confidence interval of the overall response rate in this study overlaps most of the other reported regimens. The optimal therapy for advanced urothelial cancer remains undefined.

Adult↗

PubMed2000

The evolving role of hormone therapy in advanced prostate cancer.

Earlier diagnosis and treatment of prostate cancer has changed the face of late-stage disease, and the use of mainstay hormonal therapies--orchiectomy, luteinizing hormone releasing-hormone analogs, and combined androgen ablation--are evolving rapidly. New approaches such as antiandrogen monotherapy and intermittent therapy are being evaluated. In addition, palliative treatments for patients with androgen-independent tumors have expanded. The most common clinical presentation of advanced prostate cancer is a rising prostate-specific antigen level following primary therapy (radical prostatectomy or radiotherapy or both). Due to the negative psychological implications of orchiectomy, many patients are opting for treatment with luteinizing hormone-releasing hormone analogs. Because studies of combined androgen ablation have not provided conclusive results, it is reasonable to forego antiandrogen therapy for patients who undergo bilateral orchiectomy. Management options for patients with androgen-independent prostate cancer are expanding and include antiandrogen removal, antiandrogen therapy, and glucocorticoids.

Androgen Antagonists↗

PubMed1999

Phase II trial of suramin in patients with metastatic renal cell carcinoma.

This study was conducted to assess the efficacy and toxicity of suramin administered using a fixed dose schedule in patients with advanced renal cell carcinoma. Fourteen eligible patients with advanced renal cell carcinoma were enrolled and treated on a fixed dose schedule of suramin administered over 12 weeks. Suramin was administered by intravenous infusions over 1 hour. None of the 13 evaluable patients demonstrated an objective response. Only 3 patients completed the 12-week therapy course, with the majority developing progressive disease on therapy. The fixed dosage schedule was well tolerated with minimal to moderate toxicity. Suramin in this fixed dose schedule is well tolerated but has no activity in advanced renal cell carcinoma.

Adult↗

PubMed1998

Paclitaxel plus gallium nitrate and filgrastim in patients with refractory malignancies: a phase I trial.

To determine the maximally tolerated dose of paclitaxel with and without filgrastim (G-CSF) when administered as a 24-hour intravenous infusion after a 120-hour infusion of gallium nitrate at a fixed dose of 300 mg/m2/24 hours, 40 patients were entered onto a trial lasting from September 1994 to September 1996. Eligibility included a diagnosis of an advanced malignancy not amenable to curative therapy and up to one previous chemotherapy regimen for metastatic disease. Gallium was administered at a fixed dose of 300 mg/m2/day as a continuous intravenous infusion for 120 hours. Paclitaxel starting at 90 mg/m2 was given concurrently with the last 24 hours of the gallium as a 24-hour intravenous infusion. Cycles were repeated every 21 days. Once the maximum tolerated dose (MTD) of paclitaxel was reached, G-CSF (5 microg/kg/day days 7-16) was added and paclitaxel dose escalation continued. The MTD for paclitaxel without G-CSF was 110 mg/m2 and 225 mg/m2 with G-CSF, with neutropenia being the dose-limiting toxicity. A partial response was noted in a patient who had thymoma and a complete response was achieved in a patient who had colon cancer. The recommended phase II dosage is gallium nitrate at 300 mg/m2/day over 120 hours, with paclitaxel at 110 mg/m2 over 24 hours without G-CSF or 225 mg/m2 over 24 hours with G-CSF and 0.5 mg calcitriol on days 1 through 7. Further trials of this modified regimen for outpatient administration are in progress.

Adult↗

PubMed1998

Vinblastine, ifosfamide, gallium nitrate, and filgrastim in platinum- and paclitaxel-resistant ovarian cancer: a phase II study.

The authors performed a phase II trial of the VIG regimen (vinblastine, ifosfamide, and gallium nitrate) in patients who had advanced ovarian cancer who were refractory to cisplatin and/or carboplatin and whose disease had progressed after paclitaxel-based therapy. This was a heavily pretreated population, with five patients having received two to three prior chemotherapy regimens and six patients having received more than six prior chemotherapy regimens, with an average of 21 therapy cycles per patient. Fourteen patients were treated with vinblastine, 0.08 mg/kg intravenously on days 1 and 2; ifosfamide, 900 mg/m2 intravenously on days 1 through 5 with standard mesna uroprotection; and gallium nitrate administered as a continuous intravenous infusion at 225 mg/m2 per 24 hours x 120 hours. Granulocyte colony-stimulating factor (G-CSF) was administered subcutaneously at 5 microg/kg/day beginning on day 7 until day 13. Five of 14 patients achieved a partial response for an overall response rate of 36% (95% confidence interval, 14%-68%). The median response duration was 14 weeks. Toxicity was primarily hematologic, with anemia and leukopenia being most significant. There were no treatment-related deaths. Further evaluation of this regimen in a less heavily pretreated population is warranted.

Aged↗

PubMed1997

Vinblastine, ifosfamide, and gallium nitrate--an active new regimen in patients with advanced carcinoma of the urothelium. A phase II trial of the Eastern Cooperative Oncology Group (E5892).

BACKGROUND: This study was conducted to assess the efficacy and toxicity of vinblastine, ifosfamide, and gallium nitrate (VIG) as first-line chemotherapy in patients with locally advanced or metastatic carcinoma of the urothelium. METHODS: Forty-five eligible patients were enrolled and stratified into good and poor risk groups. Poor risk was defined as age > or = 70 years, 1 functioning kidney, and prior adjuvant or neoadjuvant chemotherapy. Good risk patients were treated with vinblastine, 0.11 mg/kg, on Days 1 and 2; ifosfamide, 1.2 g/m2, on Days 1-5 with mesna uroprotection; and gallium nitrate, 300 mg/m2, as a continuous infusion on Days 1-5. Poor risk patients received similar therapy with doses decreased by 20% and administered over 4 days. All patients received recombinant human granulocyte-colony stimulating factor. Cycles were repeated at 21-day intervals until disease progression or to a maximum of 6 cycles. RESULTS: Twenty of 45 patients (44%; 95% confidence interval, 30-60%) demonstrated an objective response, with 6 patients (13%) achieving a complete clinical response. The median duration of response was 47 weeks and the median survival duration for all patients was 10 months. Hematologic toxicity was significant, with 28 patients and 31 patients experiencing Grade 3 or 4 leukopenia and anemia, respectively. Six patients had clinically significant cardiac events (primarily atrial arrhythmias). There were two early deaths that were possibly treatment related. CONCLUSIONS: VIG is an active regimen in patients with advanced urothelial carcinoma. Toxicity is significant but acceptable. Patients with significant cardiac disease (especially arrhythmias) should be treated with extra care. The 4-day regimen appears to have similar therapeutic efficacy with less toxicity.

Adenocarcinoma↗

PubMed1997

The role of radionuclide angiocardiography in the treatment of patients receiving doxorubicin-based chemotherapy: a reassessment.

We attempted to evaluate the role of radionuclide angiography in the routine treatment of patients receiving doxorubicin-based therapy in a university hospital setting. We identified 222 cancer patients treated with doxorubicin or who underwent radionuclide angiography with the intent to receive doxorubicin at the University of Iowa in 1989. We examined the cumulative doses of doxorubicin, results of radionuclide angiograms, cardiac risk factors, and clinical outcomes and survival of patients. Of 222 patients, 168 (76%) underwent at least one radionuclide angiogram and received doxorubicin. Only a baseline study was performed in 136 (81%) of these 168 patients. Only 32 underwent follow-up study during therapy; six patients discontinued therapy for an 11-21% decrease in left ventricular function. The mean dose of doxorubicin received was 211 mg/m2, and 193 patients (96%) received a cumulative dose <450 mg/m2. Only two patients (1%) had heart failure. A questionnaire sent to medical oncologists in Iowa showed that use of radionuclide angiography in our institution reflected practice throughout the state. The majority of patients in our population who underwent radionuclide angiography had a single baseline study, which provides little clinically useful information. The majority of patients receiving doxorubicin as currently employed can be safely treated without radionuclide angiography.

Adolescent↗

PubMed1997

A phase II trial of edatrexate in patients with advanced renal cell carcinoma. An Eastern Cooperative Oncology Group study.

We performed a Phase II trial of edatrexate in 44 chemotherapy-naive patients with advanced renal cell carcinoma. Prior therapy with one biological-response modifier was permitted. Most patients had multiple sites of metastatic disease and were considered to have a poor prognosis using Eastern Cooperative Oncology Group criteria. Edatrexate was administered intravenously at a dose of 80 mg/m2 weekly with 5 weeks of therapy considered one cycle. Oral cryotherapy using ice chips was administered before each edatrexate dose. Thirty-seven patients were eligible and evaluable for toxicity and response. Two patients obtained a partial response, for an overall response rate of 5.4% (95% confidence interval of 0.6%, 18.2%); one patient remained in remission at 26+ months. Three treatment-related deaths occurred. Toxicity was severe, with stomatitis, myelosuppression, and other gastrointestinal side effects most prominent. Edatrexate in this dose and schedule has minimal activity in advanced renal cell carcinoma and is toxic.

Adult↗

PubMed1997

Continuous infusion, intravesical doxorubicin for the treatment of regionally advanced bladder cancer: a phase I-II trial.

Patients with regionally advanced bladder cancer not considered candidates for definitive surgical intervention underwent continuous antegrade infusion of doxorubicin by percutaneous nephrostomy tube. Doxorubicin was administered for 7 consecutive days at a rate designed to achieve target urinary concentrations (range 5-80 micrograms/ml). Urine and serum concentrations of doxorubicin were monitored daily. Toxicity was assessed by serial renal scans, antegrade nephrostograms, blood counts, and serum chemistries. Patients were restaged after three cycles of therapy. In all, 23 cycles, constituting 156 days of therapy, were administered to 10 patients. Target urinary drug levels were achieved during all cycles. Total doxorubicin dose ranged from 125 to 2,500 mg. No systemic (neutropenia or myocardial dysfunction) or regional toxicity (extravasation, sepsis, stricture) was noted. Five of 10 patients tolerated the planned three treatment cycles. Poor performance status (PS, Eastern Cooperative Oncology Group: ECOG 3) strongly correlated with treatment intolerance and early death from disease. After three cycles of therapy, 2 of 5 evaluable patients had stable disease, I had radiographic partial response (PR) with a biopsy demonstrating extensive tumor necrosis, I had no identifiable tumor at the time of restaging transurethral resection of bladder tumor (TURBT), and a final patient with upper and lower tract carcinoma in situ (CIS) was cytologically staged NED. (no evidence of disease). These findings demonstrate the feasibility and low toxicity of this approach.

Administration, Intravesical↗