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Biomedical subjects

R J Motzer

Publications and source records attributed to R J Motzer.

At least 19 recordsLinked to original sources
PubMed2006

Targeted therapy for metastatic renal cell carcinoma.

Metastatic renal cell carcinoma (RCC) has historically been refractory to cytotoxic and hormonal agents; only interleukin 2 and interferon alpha provide response in a minority of patients. We reviewed RCC biology and explored the ways in which this understanding led to development of novel, effective targeted therapies. Small molecule tyrosine kinase inhibitors, monoclonal antibodies and novel agents are all being studied, and phase II studies show promising activity of sunitinib, sorafenib and bevacizumab. The results of phase III studies will determine the role of these agents in metastatic RCC.

Antibodies, Monoclonal↗
PubMed2004

Predicting survival of patients with metastatic renal cell carcinoma.

The relationship between pretreatment clinical features and survival was studied from patients treated on clinical trials for metastatic renal cell carcinoma (RCC) at the Memorial Sloan-Kettering Cancer Center. The primary analysis was performed on 670 patients treated with cytokines or chemotherapy, from which a multivariate model was derived to predict survival. Studies which followed addressed: (1) the survival of patients given interferon-alpha as first-line therapy; (2) a comparison of survival for patients treated with chemotherapy versus cytokine therapy; and (3) survival of patients with non-clear cell histology. Prospective identification of patients more likely to benefit from cytokine therapy is important as a stratification factor in phase III trials, and in risk-directed therapy.

Antineoplastic Agents↗
PubMed2004

The functional assessment of cancer therapy-BRM (FACT-BRM): a new tool for the assessment of quality of life in patients treated with biologic response modifiers.

PURPOSE: This paper reports on the development and validation of two biologic response modifier (BRM) subscales for use with the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) questionnaire. METHODS: Using the FACT-G as a base, 17 additional questions related to symptoms common to interferon and retinoid therapy were developed. Data collected at baseline (n = 191) and week 2 (n = 168) in a randomized trial of interferon +/- 13-cis-retinoic acid in advanced renal cell carcinoma patients were used to validate this measure. RESULTS: Using a combined empirical and conceptual approach, the 17 questions were reduced to 13 questions consisting of two subscales: 'BRM-physical' (7 items; baseline coefficient alpha(alpha) = 0.70; week-2 alpha = 0.75) and 'BRM-mental' (6 items; baseline alpha = 0.79; week-2 alpha = 0.78). Internal consistency of the trial outcome index (TOI) combining physical well-being, functional well-being and the BRM subscales, was 0.91 for baseline assessments and 0.92 for week 2. Discriminant validity was demonstrated for the TOI by its ability to differentiate among prognostic risk groups, and for the total FACT-G, TOI and total FACT-BRM scores by their ability to distinguish between groups differing in performance, response and toxicity status. CONCLUSIONS: The 'BRM-physical' and 'BRM-mental' subscales can be combined with the FACT-G to form the 'FACT BRM' scale, useful for measuring QOL in cancer patients who are receiving treatment with biologic response modifiers.

Activities of Daily Living↗
PubMed2002

Phase II trial of branched peginterferon-alpha 2a (40 kDa) for patients with advanced renal cell carcinoma.

BACKGROUND: Peginterferon-alpha 2a (40 kDa), PEGASYS(TM) (PEG-IFN), is a modified form of recombinant human interferon (IFN)-alpha 2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase II trial was conducted in previously untreated patients with advanced renal cell carcinoma (RCC) to assess efficacy, toxicity and pharmacokinetic profile. PATIENTS AND METHODS: Forty previously untreated patients with advanced RCC were enrolled on this multicenter trial. The median age was 60 years and 63% had prior nephrectomy. PEG-IFN was administered at a dose of 450 micro g/week on a weekly basis by subcutaneous injection. Serial venous blood samples were drawn to assess concentrations of PEG-IFN. RESULTS: Five (13%) patients achieved a major response (four partial and one complete). The median time to progression was 3.8 months, and 63% of patients were alive at 1 year. The toxicity profile was mostly mild to moderate in intensity. Toxicity higher than grade 2 included neutropenia (six patients), fatigue/asthenia (four patients), nausea/vomiting (three patients) and elevated hepatic transaminase concentrations (four patients). Serum drug levels were studied in all patients; mean C(max) at week 1 was 19 ng/ml, and levels were sustained at close to peak over 1 week. With chronic dosing, drug concentration was increased 3-fold, and steady state was achieved in 5-9 weeks. CONCLUSIONS: The sustained maintenance of serum levels of PEG-IFN allows once-weekly dosing. The efficacy and tolerability profile was qualitatively similar to standard IFN-alpha, and adverse events were mostly mild to moderate in nature.

2',5'-Oligoadenylate Synthetase↗
PubMed2001

Predicting outcome to chemotherapy in patients with germ cell tumors: the value of the rate of decline of human chorionic gonadotrophin and alpha-fetoprotein during therapy.

PURPOSE: The prognostic significance of the rate of decline of the serum tumor marker alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) during the first two cycles of chemotherapy in germ cell tumor (GCT) patients was initially reported by us, but its value has been debated. We re-examined this issue in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification system and investigated the role of including in the analysis patients whose markers normalized early. PATIENTS AND METHODS: One hundred eighty-nine GCT patients with elevated AFP/HCG marker values treated with platinum-based chemotherapy between 1986 and 1998 were included in this analysis. Patients were classified as good, intermediate, or poor risk by the IGCCCG criteria and as having satisfactory or unsatisfactory marker decline. Risk and marker decline were correlated with response, event-free survival, and overall survival. RESULTS: Satisfactory marker decline predicted improved complete response (CR) proportion and event-free and overall survival (P <.0001). The CR proportion, 2-year event-free, and 2-year overall survival rates for patients with a satisfactory and unsatisfactory marker decline were 92% versus 62%, 91% versus 69%, and 95% versus 72%, respectively. Marker decline remained a significant variable for all three end points when adjusted for risk (P <.01) with the outcome differences most pronounced in the poor-risk group. CONCLUSION: The rate of marker decline during chemotherapy has prognostic value independent of risk and may play a significant role in the management of poor-risk patients. It is appropriate to include patients whose markers normalized early.

Adolescent↗
PubMed2001

Low-volume nodal metastases detected at retroperitoneal lymphadenectomy for testicular cancer: pattern and prognostic factors for relapse.

PURPOSE: To determine the incidence, pattern, and predictive factors for relapse in patients with low-volume nodal metastases (stage pN1) at retroperitoneal lymphadenectomy (RPLND) and identify who may benefit from chemotherapy in the adjuvant or primary setting. PATIENTS AND METHODS: Fifty-four patients with testicular nonseminomatous germ cell tumor had low-volume retroperitoneal metastases (pathologic stage pN1, 1997 tumor-node-metastasis classification) resected at RPLND, 50 of whom were managed expectantly without adjuvant chemotherapy. The dissection was bilateral in 12 and was a modified template in 38 patients. Retroperitoneal metastases were limited to microscopic nodal involvement in 14 patients. Follow-up ranged from 1 to 106 months (median, 31.4 months). RESULTS: Eleven patients (22%) suffered a relapse at a median follow-up of 1.8 months (range, 0.6 to 28 months). The most frequent form of recurrence was marker elevation in nine (18%) patients. Persistent marker elevation after orchiectomy and before retroperitoneal lymphadenectomy was a significant independent predictor of relapse (relative risk, 8.0; 95% confidence interval, 2.3 to 27.8; P =.001). Four of five (80%) patients with elevated markers (alpha-fetoprotein alone in three, alpha-fetoprotein and beta human chorionic gonadotropin in one) suffered a relapse, compared with seven of 45 (15.6%) patients with normal markers. CONCLUSION: Clinical stage I and IIA patients with normal markers who have low-volume nodal metastases have a low incidence of relapse and can be managed by observation only if compliance can be assured. In contrast, patients with elevated markers before retroperitoneal lymphadenectomy have a high rate of relapse and should be considered for primary chemotherapy.

Actuarial Analysis↗
PubMed2001

Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with advanced renal cell carcinoma.

PURPOSE: Pegylated (40 kd) interferon alfa-2a (IFNalpha2a) (PEGASYS, Hoffman-La Roche, Nutley, NJ; PEG-IFN) is a modified form of recombinant human IFNalpha2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase I study of PEG-IFN with pharmacokinetic and pharmacodynamic evaluations was conducted in previously untreated patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-seven patients were enrolled onto cohorts of three or six patients. PEG-IFN was administered on a weekly basis by subcutaneous injection. The dose was escalated from 180 microg/wk to a maximum of 540 microg/wk in 90-microg increments. Serial venous blood samples were drawn to assess concentrations of PEG-IFN and two immunologic surrogates, neopterin and 2'-5' oligoadenylate synthetase (OAS). RESULTS: The maximum-tolerated dose was determined as 540 microg/wk, because two patients experienced dose-limiting toxicity within 28 days of starting treatment. One developed serum grade 3 ALT elevation, and a second developed grade 3 fatigue. Six patients were treated at 450 microg/wk without dose-limiting toxicity. Over the course of treatment, the side-effect profile was mostly mild to moderate in intensity. Adverse events included fatigue, fever, headache, myalgia, nausea, and decreased appetite. Five patients (19%) achieved a partial response. The mean maximum serum concentration increased from 5.0 to 27 ng/mL, and mean area under the curve increased from 247 to 2,981 ng/h/mL, with dose escalation from 180 microg/wk to 540 microg/wk. Serum concentration of PEG-IFN was sustained at close to peak during the dosing interval, and steady-state was achieved in approximately 5 weeks. The immunologic surrogates, neopterin and OAS, were induced at all doses with a sustained concentration profile similar to PEG-IFN. CONCLUSION: PEG-IFN is a modified form of IFNalpha2a with distinct pharmacokinetic advantages and immunomodulatory and antitumor activity for patients with advanced RCC. A dose of 450 microg/wk by subcutaneous administration was determined as a suitable dose for further study. PEG-IFN is more convenient to administer than IFNalpha and has potential for increased efficacy, less toxicity, or both. The efficacy and toxicity of PEG-IFN will be further assessed in clinical trials and compared with IFNalpha.

Adult↗
PubMed2001

Role of postchemotherapy adjunctive surgery in the management of patients with nonseminoma arising from the mediastinum.

PURPOSE: To evaluate the role of postchemotherapy surgery in patients with nonseminomatous germ cell tumors arising from the anterior mediastinum. PATIENTS AND METHODS: Thirty-two patients with nonseminoma arising from a mediastinal primary site were treated on a clinical trial at our center, and they underwent postchemotherapy surgery. The results of postchemotherapy surgical resection, frequency of viable tumor found during postchemotherapy surgery, and prognostic factors for survival were assessed. RESULTS: Complete resection of all gross residual disease was achieved in 27 patients (84%). Histologic analysis of resected residua postchemotherapy revealed viable tumor in 66%, teratoma in 22%, and necrosis in 12% of the specimens. Viable tumor included embryonal carcinoma, choriocarcinoma, yolk sac carcinoma, seminoma, and teratoma with malignant transformation to nongerm cell histology (eg, sarcoma). Clinical characteristics associated with a shorter survival after surgery included the presence of viable tumor in a resected specimen (P =.003) and more than one site resected during surgery (P =.06). There were no statistically significant differences in survival for patients who underwent surgical resection with normal markers compared with patients with elevated serum tumor markers (P =.33). A trend toward shorter survival was found in patients with increasing tumor markers before surgery compared with patients with normal and declining serum tumor markers (P =.09). CONCLUSION: Surgical resection of residual mass after chemotherapy plays an integral role in the management of patients with primary mediastinal nonseminoma. Teratoma and viable tumor were found in the majority of resected residua after chemotherapy. Because patients who undergo conventional salvage chemotherapy programs rarely achieve long-term disease-free status, selected patients with elevated markers after chemotherapy are considered candidates for surgical resection.

Adolescent↗
PubMed2001

Phase II trial of irofulven (6-hydroxymethylacylfulvene) for patients with advanced renal cell carcinoma.

The aim of this study was to determine the antitumor activity of irofulven (6-hydroxymethylacylfulvene) in patients with advanced renal cell carcinoma (RCC). Eligible patients had advanced renal cell carcinoma with bidimensionally measurable disease, a Karnofsky performance status of at least 70, life expectancy of greater than three months, no prior treatment with chemotherapy, and no evidence of brain metastases. Irofulven was administered at a dose of 11 mg/m2 by 5-min intravenous infusion, on 5 consecutive days. Cycles were repeated every 28 days. Thirteen patients were enrolled in this study and 12 were evaluable for response. Of the twelve evaluable patients, no major responses were achieved. Eight patients had stable disease as best response. Toxicity included myelosuppression and gastrointestinal side effects. At the dose and schedule used in this trial, irofulven did not produce clinical response in RCC.

Adult↗
PubMed2001

Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma.

Recombinant human interleukin-12 (rHuIL-12) is a pleiotropic cytokine with anticancer activity against renal cell carcinoma (RCC) in preclinical models and in a phase I trial. A randomized phase II study of rHuIL-12 compared with interferon-alpha (IFN-alpha) evaluated clinical response for patients with previously untreated, advanced RCC. Patients were randomly assigned 2:1 to receive either rHuIL-12 or IFN-alpha2a. rHuIL-12 was administered by subcutaneous (s.c.) injection on days 1, 8, and 15 of each 28-day cycle. The dose of IL-12 was escalated during cycle 1 to a maintenance dose of 1.25 microg/kg. IFN was administered at 9 million units by s.c. injection three times per week. Serum concentrations of IL-12, IFN-gamma, IL-10, and neopterin were obtained in 10 patients treated with rHuIL-12 after the first full dose of 1.25 microg/kg given on day 15 (dose 3) of cycle 1 and again after multiple doses on day 15 (dose 6) of cycle 2. Thirty patients were treated with rHuIL-12, and 16 patients were treated with IFN-alpha. Two (7%) of 30 patients treated with rHuIL-12 achieved a partial response, and the trial was closed to accrual based on the low response proportion. IL-12 was absorbed rapidly after s.c. drug administration, with the peak serum concentration appearing at approximately 12 h in both cycles. Serum IL-12 concentrations remained stable on multiple dosing. Levels of IFN-gamma, IL-10, and neopterin increased with rHuIL-12 and were maintained in cycle 2. rHuIL-12 is a novel cytokine with unique pharmacologic and pharmacodynamic features under study for the treatment of malignancy and other medical conditions. The low response proportion associated with rHuIL-12 single-agent therapy against metastatic RCC was disappointing, given the preclinical data. Further study of rHuIL-12 for other medical conditions is underway. For RCC, the study of new cytokines is of the highest priority.

Adult↗
PubMed2001

A postoperative prognostic nomogram for renal cell carcinoma.

PURPOSE: Few published studies have combined prognostic factors to predict the likelihood of recurrence after surgery for renal cell carcinoma. We developed a nomogram for this purpose. MATERIALS AND METHODS: With Cox proportional hazards regression analysis, we modeled pathological data and disease followup for 601 patients with renal cell carcinoma who were treated with nephrectomy. Predictor variables were patient symptoms, including incidental, local or systemic, histology, including chromophobe, papillary or conventional, tumor size, and pathological stage. Treatment failure was recorded when there was either clinical evidence of disease recurrence or death from disease. Validation was performed with a statistical (bootstrapping) technique. RESULTS: Disease recurrence was noted in 66 of the 601 patients, and those in whom treatment was successful had a median and maximum followup of 40 and 123 months, respectively. The 5-year probability of freedom from failure for the patient cohort was 86% (95% confidence interval 82 to 89). With statistical validation, predictions by the nomogram appeared accurate and discriminating with an area under the receiver operating characteristic curve, that is a comparison of the predicted probability with the actual outcome of 0.74. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among patients with newly diagnosed renal cell carcinoma. The nomogram may be useful for patient counseling, clinical trial design and patient followup planning.

Carcinoma, Renal Cell↗
PubMed2000

Phase II trial of pyrazoloacridine in patients with cisplatin-refractory germ cell tumors.

Thirteen patients with cisplatin-refractory germ cell tumors were treated on a Phase II trial with pyrazoloacridine. Pyrazoloacridine was given intravenously at 600 mg/m2 every three weeks. The median nadir leucocyte count was 2.5 cells/mm3, hemoglobin was 10.8 g/dl, and platelet count was 126,000 cells/m3. None of the thirteen evaluable patients achieved a major response. Pyrazoloacridine is not efficacious in the treatment of cisplatin-refractory germ cell tumors.

Acridines↗
PubMed2000

Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer.

PURPOSE: To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m(2), and cisplatin 100 mg/m(2) were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m(2); the largest dose was selected for the phase II part of the trial. RESULTS: Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity. CONCLUSION: Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.

Adult↗
PubMed2000

Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma.

PURPOSE: A randomized phase III trial was conducted to determine whether combination therapy with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFNalpha2a) is superior to IFNalpha2a alone in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Two hundred eighty-four patients were randomized to treatment with IFNalpha2a plus 13-CRA or treatment with IFNalpha2a alone. IFNalpha2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU (by increments of 3 MU), unless >/= grade 2 toxicity occurred, in which case dose escalation was stopped. Patients randomized to combination therapy were given oral 13-CRA 1 mg/kg/d plus IFNalpha2a. Quality of life (QOL) was assessed. RESULTS: Complete or partial responses were achieved by 12% of patients treated with IFNalpha2a plus 13-CRA and 6% of patients treated with IFNalpha2a (P =.14). Median duration of response (complete and partial combined) in the group treated with the combination was 33 months (range, 9 to 50 months), versus 22 months (range, 5 to 38 months) for the second group (P =.03). Nineteen percent of patients treated with IFNalpha2a plus 13-CRA were progression-free at 24 months, compared with 10% of patients treated with IFNalpha2a alone (P =.05). Median survival time for all patients was 15 months, with no difference in survival between the two treatment arms (P =.26). QOL decreased during the first 8 weeks of treatment, and a partial recovery followed. Lower scores were associated with the combination therapy. CONCLUSION: Response proportion and survival did not improve significantly with the addition of 13-CRA to IFNalpha2a therapy in patients with advanced RCC. 13-CRA may lengthen response to IFNalpha2a therapy in patients with IFNalpha2a-sensitive tumors. Treatment, particularly the combination therapy, was associated with a decrease in QOL.

Administration, Oral↗
PubMed2000

Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients.

PURPOSE: To evaluate the efficacy and toxicity of sequential, dose-intensified chemotherapy with paclitaxel/ifosfamide and carboplatin/etoposide administered plus peripheral blood-derived stem-cell (PBSC) support for patients with germ cell tumors (GCT) who have unfavorable prognostic features in response to conventional-dose salvage programs. Carboplatin was dose escalated by target area under the curve (AUC; in [milligrams per milliliter] x minutes) among patient cohorts, and pharmacokinetic studies were performed for comparison. PATIENTS AND METHODS: Thirty-seven previously treated patients who had cisplatin-resistant GCT and unfavorable prognostic features for response to conventional-dose salvage therapy were treated. Two cycles of paclitaxel 200 mg/m(2) plus ifosfamide 6 g/m(2) were given 2 weeks apart with leukapheresis, followed by three cycles of carboplatin plus etoposide given 14 to 21 days apart with reinfusion of PBSCs. The dose of etoposide was 1, 200 mg/m(2), and the carboplatin target AUC ranged among cohorts from 12 to 32 (mg/mL) x min. Pharmacokinetic studies of carboplatin were performed for comparison of target to measured AUC. RESULTS: Twenty-one patients (57%) achieved a complete response and an additional two patients (5%) achieved a partial response with normal tumor markers; therefore, 23 (62%) achieved a favorable response. Eight patients relapsed, and 15 (41%) of the favorable responses remained durable at a median follow-up of 30 months. Myelosuppression was the major toxicity; 58% of carboplatin/etoposide cycles were associated with hospitalization for nadir fever. The AUC of carboplatin measured in serum was lower than the target AUC; this may be related to underestimation of the glomerular filtration rate used in the dosing formula. CONCLUSION: Dose-intense therapy with sequential, accelerated chemotherapy of paclitaxel/ifosfamide and carboplatin/etoposide administered with PBSC support was relatively well tolerated. The durable complete response proportion was substantial in patients with unfavorable prognostic features for achieving durable complete response to conventional-dose salvage programs. Optimal dosing of carboplatin in the high-dose setting warrants further investigation.

Adolescent↗
PubMed2000

Effect of cytokine therapy on survival for patients with advanced renal cell carcinoma.

PURPOSE: To evaluate the relationship between treatment with cytokine therapy and survival, investigate the effect of nephrectomy on survival, and identify long-term survivors among a cohort of 670 patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: A total of 670 patients with advanced RCC treated on 24 clinical trials of systemic chemotherapy or cytokine therapy were the subjects of this retrospective analysis. Treatment was categorized as cytokine (containing interferon alfa and/or interleukin-2) in 396 patients (59%) and as chemotherapy (cytotoxic or hormonal therapy) in 274 (41%). Among the 670 patients, those with survival times of greater than 5 years were identified as long-term survivors. RESULTS: Patients treated with cytokine therapy had a longer survival time than did those treated with chemotherapy, regardless of the year of treatment or risk category based on pretreatment features. The median survival times for favorable-, intermediate-, and poor-risk patients were 27, 12, and 6 months for those treated with cytokines and 15, 7, and 3 months for those treated with chemotherapy, respectively. The magnitude of difference in median survival was greater in the favorable- and intermediate-risk groups. The median survival time was less than 6 months in the poor-risk group for both treatment programs. Median survival time was 14 months among patients with prior nephrectomy plus time from diagnosis to treatment greater than 1 year versus 8 months among those with time from diagnosis to treatment less than 1 year, regardless of pretreatment nephrectomy status. Thirty patients (4.5%) among the 670 patients were identified as long-term survivors; 12 were free of disease after nephrectomy and treatment with interferon alfa, interleukin-2, or surgical resection of metastasis. CONCLUSION: The low proportion of patients with advanced RCC who achieve long-term survival emphasizes the need for clinical investigation to identify more effective therapy.

Adolescent↗
PubMed2000

Systemic therapy for renal cell carcinoma.

PURPOSE: We review the status of systemic therapy for patients with advanced renal cell carcinoma. MATERIALS AND METHODS: A literature search was performed on MEDLINE and CANCERLIT to identify results of systemic therapy for patients with renal cell carcinoma published from January 1990 through December 1998. Treatment results of chemotherapy agents, immunotherapy, combination programs and adjuvant therapy were reviewed. RESULTS: No chemotherapy agent has produced response rates that justify its use as a single agent. Interferon-alpha and interleukin (IL)-2 demonstrated low response rates ranging from 10% to 20%. The results of 2 randomized trials suggest that treatment with interferon-alpha compared to vinblastine or medroxyprogesterone achieves a small improvement in survival. Response rates in patients treated with low dose IL-2 are similar to those achieved with a high dose bolus schedule but whether the responses are as durable is being addressed in an ongoing randomized trial. A randomized trial of interferon-alpha plus IL-2 compared to monotherapy with either agent showed increased toxicity but no improvement in survival. In 3 randomized trials no survival benefit was associated with adjuvant interferon-alpha therapy following complete resection of locally advanced renal cell carcinoma. CONCLUSIONS: Despite extensive evaluation of many different treatment modalities, metastatic renal cell carcinoma remains highly resistant to systemic therapy. A few patients exhibit complete or partial responses to interferon and/or IL-2 but most do not respond, and there are few long-term survivors. Preclinical research, and clinical evaluation of new agents and treatment programs to identify improved antitumor activity against metastases remain the highest priorities in this refractory disease.

Carcinoma, Renal Cell↗