共查询到20条相似文献,搜索用时 15 毫秒
1.
Chris H Takimoto Scot C Remick Sunil Sharma Sridhar Mani Ramesh K Ramanathan James Doroshow Anne Hamilton Daniel Mulkerin Martin Graham Graham F Lockwood Percy Ivy Merrill Egorin Barbara Schuler Denis Greenslade Andrew Goetz Ronald Knight Rebecca Thomas Brian P Monahan William Dahut Jean L Grem 《Journal of clinical oncology》2003,21(14):2664-2672
PURPOSE: This study was undertaken to determine the toxicities, pharmacokinetics, and maximum tolerated doses of oxaliplatin in patients with renal impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. PATIENTS AND METHODS: Thirty-seven adult cancer patients with variable renal function received intravenous oxaliplatin at 60 to 130 mg/m2 every 3 weeks. Patients were stratified by 24-hour creatinine clearance (CrCL) into four cohorts: group A (controls, CrCL > or =60 mL/min), group B (mild dysfunction, CrCL 40 to 59 mL/min), group C (moderate dysfunction, CrCL 20 to 39 mL/min), and group D (severe dysfunction, CrCL <20 mL/min). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. RESULTS: No dose-limiting toxicities were observed in any patient group during the first cycle of therapy. Escalation of oxaliplatin to the maximum dose of 130 mg/m2 was well tolerated in all patient groups with a CrCL > or =20 mL/min (groups A, B, and C). Pharmacokinetic analysis showed that patients with decreased CrCL had a corresponding decrease in the clearance of plasma ultrafiltrable platinum (r2 = 0.765). However, oxaliplatin-induced side effects were not more common or severe in patients with mild to moderate renal dysfunction, despite the decrease in ultrafiltrable platinum clearance. CONCLUSION: Oxaliplatin at 130 mg/m2 every 3 weeks is well tolerated by patients with mild to moderate degrees of renal dysfunction. These data strongly support the recommendation that dose reductions of single-agent oxaliplatin are not necessary in patients with a CrCL greater than 20 mL/min. 相似文献
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Timothy W Synold Chris H Takimoto James H Doroshow David Gandara Sridhar Mani Scot C Remick Daniel L Mulkerin Anne Hamilton Sunil Sharma Ramesh K Ramanathan Heinz Josef Lenz Martin Graham Jeffrey Longmate Bennett M Kaufman Percy Ivy 《Clinical cancer research》2007,13(12):3660-3666
PURPOSE: To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patients with hepatic impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. EXPERIMENTAL DESIGN: Sixty adult cancer patients with variable hepatic function received i.v. oxaliplatin ranging from 60 to 130 mg/m(2) every 3 weeks. Patients were stratified by levels of total bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (AP) into five cohorts based on the degree of hepatic dysfunction: control group A [bilirubin, AST, and AP < or = upper limit of normal (ULN)], mild dysfunction group B (bilirubin < or = ULN, ULN < AST < or = 2.5 x ULN, or ULN < AP < or = 5 x ULN), moderate dysfunction group C (ULN < bilirubin < or = 3.0 mg/dL, AST > 2.5 x ULN, or AP > 5 x ULN), severe dysfunction group D (bilirubin > 3.0 mg/dL, any AST, and any AP), and liver transplantation group E (any bilirubin, any AST, and any AP). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. RESULTS: Dose escalation of single-agent oxaliplatin to 130 mg/m(2) was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patients with a diagnosis of laryngeal carcinoma and cervical adenocarcinoma experienced partial responses lasting 3 and 5.5 months. CONCLUSIONS: Oxaliplatin at 130 mg/m(2) every 3 weeks was well tolerated in all patients with impaired liver function. Dose reductions of single-agent oxaliplatin are not indicated in patients with hepatic dysfunction. 相似文献
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Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function. 总被引:1,自引:0,他引:1
Chris H Takimoto Martin A Graham Graham Lockwood Chee M Ng Andrew Goetz Dennis Greenslade Scot C Remick Sunil Sharma Sridhar Mani Ramesh K Ramanathan Timothy W Synold James H Doroshow Anne Hamilton Daniel L Mulkerin Percy Ivy Merrill J Egorin Jean L Grem 《Clinical cancer research》2007,13(16):4832-4839
PURPOSE: To characterize the pharmacokinetics and pharmacodynamics of oxaliplatin in cancer patients with impaired renal function. EXPERIMENTAL DESIGN: Thirty-four patients were stratified by 24-h urinary creatinine clearance (CrCL) into four renal dysfunction groups: group A (control, CrCL, >or=60 mL/min), B (mild, CrCL, 40-59 mL/min), C (moderate, CrCL, 20-39 mL/min), and D (severe, CrCL, <20 mL/min). Patients were treated with 60 to 130 mg/m2 oxaliplatin infused over 2 h every 3 weeks. Pharmacokinetic monitoring of platinum in plasma, plasma ultrafiltrates, and urine was done during cycles 1 and 2. RESULTS: Plasma ultrafiltrate platinum clearance strongly correlated with CrCL (r2 = 0.712). Platinum elimination from plasma was triphasic, and maximal platinum concentrations (Cmax) were consistent across all renal impairment groups. However, only the beta-half-life was significantly prolonged by renal impairment, with values of 14.0 +/- 4.3, 20.3 +/- 17.7, 29.2 +/- 29.6, and 68.1 h in groups A, B, C, and D, respectively (P = 0.002). At a dose level of 130 mg/m2, the area under the concentration time curve increased in with the degree of renal impairment, with values of 16.4 +/- 5.03, 39.7 +/- 11.5, and 44.6 +/- 14.6 mug.h/mL, in groups A, B, and C, respectively. However, there was no increase in pharmacodynamic drug-related toxicities. Estimated CrCL using the Cockcroft-Gault method approximated the measured 24-h urinary CrCL (mean prediction error, -5.0 mL/min). CONCLUSIONS: Oxaliplatin pharmacokinetics are altered in patients with renal impairment, but a corresponding increase in oxaliplatin-related toxicities is not observed. 相似文献
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The Clinical Trials Group of the National Cancer Institute of Canada (NCIC) studied single-agent epirubicin in 40 previously untreated patients with extensive small-cell lung cancer (SCLC). The starting dose of epirubicin was 100 (eight patients) or 120 (32 patients) mg/m2 administered intravenously every 3 weeks. Twenty patients (50%) achieved an objective response (95% confidence limits, 33% to 66%) and three of the 20 had complete responses (CRs). The median survival of all 40 patients was 8.3 months (35.4 weeks). Myelosuppression, mild or moderate nausea and vomiting, and hair loss were commonly seen. There was one chemotherapy-related death. This drug is active and well tolerated in SCLC and the use of it as first-line therapy did not appear to compromise survival in this group of patients. 相似文献
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Advanced transitional-cell carcinoma of the bladder is the most common cancer of the urinary tract, with a high mortality rate. Cisplatin-based chemotherapy has demonstrated prolonged survival of these patients and is considered the standard of care. Nevertheless, 40-50% of patients have impaired renal function that precludes the use of cisplatin. The non-nephrotoxic platinum analogue, carboplatin, has emerged as the most popular alternative in this setting, used mainly in doublets. However, it has not shown similar efficacy to cisplatin. In this article, platinum-based or platinum-free regimens, monotherapies or combination therapies are discussed as treatment options for this population. Their efficacy and toxicity are also being analyzed. The study of newer targeted therapies in the treatment of bladder cancer is also discussed, as are future perspectives and a five-year view in the treatment of the disease in patients with renal impairment. 相似文献
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W K Evans E Eisenhauer P Hughes J A Maroun J Ayoub F A Shepherd R Feld 《British journal of cancer》1988,58(4):464-468
Thirty-four previously untreated patients with extensive small cell lung cancer were treated with a combination of carboplatin 300 mg m-2 i.v. on day 1 and etoposide 100 mg m-2 i.v. on days 1, 2 and 3 every 28 days. Thirty-two patients were assessable for response. Eighteen patients (56%) achieved an objective response (95% confidence limits 38%-73%). Five (16%) had a complete response and 13 (41.0%) had a partial response. The median time to response was 7.8 weeks and the median duration of response was 23.1 weeks (range 6.2 to 54 weeks). The median survival of all 34 extensive disease patients was 34.7 weeks (range 1.3-59.3 weeks). Myelosuppression (leukopenia) was the main toxicity. There was one early death that may have been treatment-related. Biochemical renal dysfunction was noted in two patients. Paresthesiae and tinnitus/hearing loss were described by three and two patients respectively. Serious gastrointestinal toxicity was infrequent. This and other studies have shown this combination to be active and well tolerated in small cell lung cancer; however, it is not yet clear if it is as efficacious as the more commonly used VP-16-cisplatin regimen. 相似文献
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Crump M Couban S Meyer R Rudinskas L Zanke B Gluck S Maksymiuk A Hoskins P Matthews S Eisenhauer E 《Leukemia & lymphoma》2002,43(8):1581-1587
Preliminary results indicate that inhibitors of the nuclear enzyme topoisomerase (topo) I, such as topotecan, may be active in non-Hodgkin's lymphoma (NHL). Pre-clinical studies have shown sequential administration of a topo I and II inhibitor has supra-additive anti-tumor effects in some model systems, and that greater cytotoxicity occurs if the topo I inhibitor is given first. We enrolled, 22 eligible patients with relapsed or refractory intermediate grade NHL in a phase II study ofsequential administration of topotecan 1.25 mg/m2 days 1-5 and etoposide 50 mg po b.i.d. days 6-12, every 28 days without G-CSF. Most patients had diffuse large B-cell lymphoma and all had received only one prior regimen (CHOP, 20 patients, or equivalent, 2 patients). Patients with stable or responding disease were allowed to proceed to high-dose therapy and autologous stem-cell transplant after 2 cycles of therapy. The 22 patients received a total of 62 cycles of topotecan + etoposide (median 2, range 1-6), and 4/22 completed all six planned cycles. Hematologic toxicity was significant and resulted in incomplete etoposide dosing in half of all cycles in 16/22 patients. Nineteen of twenty-two patients had grade 3/4 neutropenia, 12 had grade 3/4 thrombocytopenia, and 6 grade 3/4 anemia. Eleven patients had at least one episode of febrile neutropenia or had documented infection. Non-hematologic toxicity was mild. Four patients had a partial response (PR) (18.2%), nine had stable disease and seven progressed; three patients with stable disease went on to ABMT. The combination of topotecan and etoposide as given in this study has modest activity in relapsed/refractory aggressive histology NHL, and produces marked myelosuppression. Other doses and schedules combining topo I and II inhibitors, or topo I inhibitors with alkylating agents, should be explored with the addition of hematopoietic growth factors in this patient population. 相似文献
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A Belch C T Kouroukis M Crump L Sehn R D Gascoyne R Klasa J Powers J Wright E A Eisenhauer 《Annals of oncology》2007,18(1):116-121
BACKGROUND: We evaluated the activity and toxic effects of bortezomib in patients with mantle cell lymphoma. PATIENTS AND METHODS: Thirty patients, including 29 eligible patients, were enrolled; 13 had received no prior chemotherapy. The dose of bortezomib was 1.3 mg/m2 given on days 1, 4, 8 and 11 every 21 days. Response was assessed according to the International Workshop Criteria for non-Hodgkin's lymphoma and toxicity graded using the National Cancer Institute Common Toxicity Criteria version 2.0. RESULTS: There were 13 responding patients (46.4%; 95% confidence interval=27.5% to 66.1%), including one unconfirmed complete remission. The median response duration was 10 months. Response rates were similar in previously untreated (46.2%) and treated (46.7%) patients. Neurological toxicity and myalgia led to treatment discontinuation in 10 patients after two to seven treatment cycles. Five serious adverse events (including two deaths) associated with fluid retention were observed in the first 12 patients. We subsequently excluded patients with baseline effusions, dyspnea or edema; no further events were seen. CONCLUSIONS: Bortezomib is active in treating patients with mantle cell lymphoma. While cumulative neuromuscular toxic effects limited therapy duration and specific issues related to fluid retention require further evaluation, continued study of this drug in combination regimens is warranted. 相似文献
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Mertens W. C.; Eisenhauer E. A.; Moore M.; Venner P.; Stewart D.; Muldal A.; Wong D. 《Annals of oncology》1993,4(4):331-332
BACKGROUND:: Gemcitabine (2', 2'-difluorodeoxycytidine; dFdC) an anticanceragent with activity in preclinical models, was felt to be apromising new chemotherapy drug which warranted testing in patientswith advanced renal cell carcinoma METHODS:: Eighteen patients with histologically proven metastatic or locallyrecurrent renal cell carcinoma and bidimensionally measurabledisease were accrued to a phase II study of gemcitabine administeredintravenously on days 1, 8 and 15 of a 28 day treatment cycle.Initial doses of gemcitabine were 800 mg/m2; doses in subsequentcycles were escalated to a maximum of 1250 mg/m2, toxicity permitting. RESULTS:: One partial response was seen for a response rate of 6%. Hematologictoxicity was not severe with this dosing schedule; however,two patients developed dyspnea with bronchospasm after repeatedinjections of drug. CONCLUSIONS:: The dose and schedule of gemcitabine employed results in onlya modest response rate in patients with advanced renal carcinoma.Investigators should be aware of the possibility of dyspneaand bronchospasm developing shortly after gemcitabine administration. bronchospasm, clinical trial, dyspnea, gemcitabine, renal cell carcinoma, toxicity, 2',2'-difluorodeoxycytidine 相似文献
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Meira Epplein Ksenia P Koon Scott D Ramsey John D Potter 《Journal of clinical oncology》2005,23(21):4713-4718
PURPOSE: Anecdotal reports suggest that the volume of services offered to individuals concerned with hereditary cancer risk has increased substantially in recent years. As a follow-up to our 1993 survey, we sought to determine how the scope and volume of genetic services has changed between 1993 and 2002. METHODS: We surveyed the 61 National Cancer Institute-designated cancer centers in operation in 2002 using an updated version of the questionnaire from 1993. Analysis included frequencies and summary statistics. RESULTS: The majority of cancer centers responding (46 of 56 centers; 82.1%) provided some genetic services for evaluation of familial cancer, which is a higher proportion than in 1993 (50%; P < .01). Almost all centers (42 of 46 centers; 91.3%) provided services not only to cancer patients and their families, but also to individuals concerned with risk, which is a change (P = .01) from 1993, when 64.7% of centers offered such services. In addition, increases have been found for most other measures of services rendered for familial genetic services. CONCLUSION: As public awareness of cancer susceptibility genes has grown markedly in recent years, the demand has also grown for genetic services to assess familial cancer risk. Major deleterious genetic mutations are rare, and much of the current research in genetic variation focuses on higher prevalence variants that carry lower risks. This may suggest that testing for mutations will move from genetics clinics to primary care and specialty practices. Thus, it is unclear whether the scope and volume of cancer center genetics services will continue to grow as rapidly as they have over the last decade. 相似文献
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《Annals of oncology》2013,24(11):2922-2926
BackgroundPre-clinical data have suggested a therapeutic role of Hedgehog (Hh) pathway inhibitors in chondrosarcoma.MethodsThis phase II trial included patients with progressive advanced chondrosarcoma. They received GDC-0449 150 mg/day (days 1–28, 28-day cycle). The primary end point was the 6-month clinical benefit rate (CBR) defined as the proportion of patients with non-progressive disease at 6 months. A 6-month CBR of 40% was considered as a reasonable objective to claim drug efficacy.ResultsBetween February 2011 and February 2012, 45 patients were included. Twenty had received prior chemotherapy. Thirty-nine were assessable for efficacy. The 6-month CBR was 25.6% (95% confidence interval 13.0–42.1). All stable patients had grade 1 or 2 conventional chondrosarcoma with documented progression within the 6 months before inclusion. All but one with available data also had overexpression of the Hh ligand. Median progression-free and overall survivals were 3.5 and 12.4 months, respectively. The most frequent adverse events were grade 1 or 2 myalgia, dysgeusia and alopecia.ConclusionsGDC-0449 did not meet the primary end point of this trial. Results suggest some activity in a subset of patients with progressive grade 1 or 2 conventional chondrosarcoma. Further studies assessing its role in combination with chemotherapy are warranted.ClinicalTrials.gov IdentifierNCT01267955. 相似文献
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F. A. Shepherd M. R. Johnston D. Payne R. Burkes J. Deslauriers Y. Cormier L. D. de Bedoya J. Ottaway K. James B. Zee 《British journal of cancer》1998,78(5):683-685
Thirty-one patients with stage IIIA (N2) non-small-cell lung cancer were randomized to receive radiotherapy alone or chemotherapy with cisplatin and vinblastine followed by surgery. Response rates to induction chemotherapy and radiotherapy were 50% and 53.3% respectively. Complete surgical resection was possible for 62.5% of patients. Median survival times were 16.2 and 18.7 months for radiotherapy alone and chemotherapy-surgery respectively (P = Ns), with no long-term improvement in survival seen with combined-modality treatment. 相似文献
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Richard L Schilsky Donna Bertucci Nicholas J Vogelzang Hedy L Kindler Mark J Ratain 《Journal of clinical oncology》2002,20(2):582-587
PURPOSE: The goals of this phase I study were to determine the maximum-tolerated doses of capecitabine and gemcitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT) and safety profile of this combination. PATIENTS AND METHODS: Eligible patients had advanced solid tumors that had failed to respond to standard therapy or for which no standard therapy was available, measurable or assessable disease, Karnofsky performance status > or = 70%, and acceptable organ function. Capecitabine was administered twice daily by mouth each day for 21 consecutive days followed by a 1-week break. Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break. RESULTS: Forty patients were enrolled onto the study, and 33 are fully assessable for toxicity. The most common toxicities during the first cycle of chemotherapy were neutropenia and mucositis. Only one patient treated at gemcitabine and capecitabine doses of 800 and 2000 mg/m(2), respectively, met protocol-specified DLT criteria; however, at these doses 65% of successive cycles required dose reduction or delay for toxicity. No episodes of DLT were observed at gemcitabine and capecitabine doses of 1,000 and 1,660 mg/m(2), respectively, and 70% of cycles of therapy were delivered without dose reduction or delay. Therefore, these doses are recommended for further study. Tumor responses were observed in patients with metastatic colorectal and pancreatic cancer. CONCLUSION: Gemcitabine and capecitabine can be combined with acceptable toxicity at nearly full doses. Antitumor activity of the combination merits further investigation in phase II studies. 相似文献
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C A Townsley K Chi D S Ernst K Belanger I Tannock G A Bjarnason D Stewart R Goel J D Ruether L L Siu J Jolivet L McIntosh L Seymour M J Moore 《Journal of clinical oncology》2003,21(8):1524-1529
PURPOSE: A multi-institution phase II study was undertaken by National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of intravenous troxacitabine (Troxatyl; Shire Pharmaceuticals Plc, Laval, Quebec, Canada), in patients with renal cell carcinoma. PATIENTS AND METHODS: Between June 1999 and March 2000, 35 patients (24 male) with a mean age of 60 years who had advanced and/or metastatic disease were treated with troxacitabine given as an intravenous infusion over 30 minutes at a dose of 10 mg/m2 intravenously, once every 3 weeks. RESULTS: Of the 33 of 35 patients evaluable for response, there were two confirmed partial responses, 21 patients had stable disease (median duration, 4.4 months), and 10 patients had progressive disease. Eight patients remained stable for more than 6 months, of whom six remain free of progression. The most common drug-related nonhematologic toxicities observed were skin rash (77.1%), hand-foot syndrome (68.6%), alopecia (51.4%), fatigue (51.4%), and nausea (57.1%). Out of a total of 145 cycles of treatment, 98 were given without steroid premedication, whereas 47 cycles were given with steroid premedication. Without premedication, skin rash occurred in 37% of cycles compared with 26% when steroids were given prophylactically. CONCLUSION: Troxacitabine given at a dose of 10 mg/m2 once every 3 weeks was well tolerated in patients with metastatic renal cell cancer, with common toxicities being a moderate to severe granulocytopenia and skin rash. Steroid premedication may reduce the frequency and severity of the skin rash. Our current study suggests that the nucleoside analog troxacitabine may have modest activity against renal cell carcinoma; however, larger studies are required to confirm this. 相似文献
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K Swenerton J Jeffrey G Stuart M Roy G Krepart J Carmichael P Drouin R Stanimir G O'Connell G MacLean 《Journal of clinical oncology》1992,10(5):718-726
PURPOSE: Given the potential for improved tolerance, a trial was initiated to compare the toxicity and efficacy of a standard regimen of cisplatin-cyclophosphamide (75 mg/m2 and 600 mg/m2, respectively) with an experimental regimen of carboplatin-cyclophosphamide (300 mg/m2 and 600 mg/m2, respectively) in women with postoperative macroscopic residual ovarian cancer. PATIENTS AND METHODS: Between 1985 and 1989, 447 (417 eligible) patients were randomized. Treatment arms were well balanced; most patients had stage III (82%), grade 3 (54%) tumors with bulky residual (greater than 2 cm in 59%), and good performance status (Eastern Cooperative Oncology Group [ECOG] 0 or 1, 77%). Response was assessed after six 4-week cycles. RESULTS: The treatments were equally deliverable, with 76% of patients completing their allocated regimen. The reported reasons for failure to complete treatment differed; toxicity/refusal predominated on the cisplatin arm, and progressive disease predominated on the carboplatin arm (P = .0092). Cisplatin-treated patients were more likely to develop neuropathy and nephropathy, and carboplatin patients experienced myelosuppression, particularly thrombocytopenia. Efficacy was similar, with no significant differences for the cisplatin and carboplatin arms in clinical response rate (57% v 59% in those with measurable disease), pathologic response rate (52% v 54% in those suitable for relaparotomy), time to progression (median, 56 v 58 weeks), or overall survival (median, 100 weeks v 110 weeks). Time to progression and survival were predicted by residual disease size, performance status, and treatment center (with those treated at centers that accrued more patients doing better). CONCLUSION: Neither regimen is optimal in that relapse remains the norm. It may be inappropriate to expect that any single regimen can be an effective therapy for all patients with advanced ovarian cancer. Both cisplatin and carboplatin are likely to have a role in future treatment strategies. 相似文献