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971.
Alex Sparreboom Charity D Scripture Vuong Trieu Paul J Williams Tapas De Andrew Yang Bridget Beals William D Figg Michael Hawkins Neil Desai 《Clinical cancer research》2005,11(11):4136-4143
PURPOSE: To compare the preclinical and clinical pharmacokinetic properties of paclitaxel formulated as a Cremophor-free, albumin-bound nanoparticle (ABI-007) and formulated in Cremophor-ethanol (Taxol). EXPERIMENTAL DESIGN: ABI-007 and Taxol were given i.v. to Harlan Sprague-Dawley male rats to determine pharmacokinetic and drug disposition. Paclitaxel pharmacokinetic properties also were assessed in 27 patients with advanced solid tumors who were randomly assigned to treatment with ABI-007 (260 mg/m(2), 30 minutes; n = 14) or Taxol (175 mg/m(2), 3 hours; n = 13), with cycles repeated every 3 weeks. RESULTS: The volume of distribution at steady state and clearance for paclitaxel formulated as Cremophor-free nanoparticle ABI-007 were significantly greater than those for paclitaxel formulated with Cremophor (Taxol) in rats. Fecal excretion was the main elimination pathway with both formulations. Consistent with the preclinical data, paclitaxel clearance and volume of distribution were significantly higher for ABI-007 than for Taxol in humans [21.13 versus 14.76 L/h/m(2) (P = 0.048) and 663.8 versus 433.4 L/m(2) (P = 0.040), respectively]. CONCLUSIONS: Paclitaxel formulated as ABI-007 differs from paclitaxel formulated as Taxol, with a higher plasma clearance and a larger volume of distribution. This finding is consistent with the absence of paclitaxel-sequestering Cremophor micelles after administration of ABI-007. This unique property of ABI-007 could be important for its therapeutic effectiveness. 相似文献
972.
Chemotherapy induces the expression of cyclooxygenase-2 in non-small cell lung cancer. 总被引:2,自引:0,他引:2
Nasser K Altorki Jeffrey L Port Fan Zhang Dragan Golijanin Howard T Thaler Anna J Duffield-Lillico Kotha Subbaramaiah Andrew J Dannenberg 《Clinical cancer research》2005,11(11):4191-4197
PURPOSE: To determine the effect of taxane-based chemotherapy on intratumoral levels of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Lung specimens obtained at the time of surgery were used to measure levels of COX-2 and PGE(2) in tumors and adjacent nontumorous tissues in three subsets of NSCLC patients who underwent: (A) surgical resection only (n = 16); (B) surgical resection after preoperative taxane-based chemotherapy (n = 13); or (C) surgical resection after preoperative chemotherapy coadministered with the selective COX-2 inhibitor, celecoxib 400 mg bid (n = 17). RESULTS: Levels of intratumoral PGE(2) were nearly 3-fold higher among patients who received preoperative chemotherapy compared with those treated by surgery alone (P < 0.001). This difference was abrogated by the addition of celecoxib to preoperative chemotherapy (P < 0.001). Amounts of intratumoral COX-2 were approximately 3-fold higher in groups of patients who received preoperative chemotherapy with celecoxib (P < 0.0001) or without celecoxib (P < 0.001), compared with the group who underwent surgical resection only. Importantly, statistically significant positive correlations between COX-2 and PGE(2) were observed in the surgery only (r = 0.502, P = 0.047) and preoperative chemotherapy groups (r = 0.740, P = 0.004); this correlation was abrogated when celecoxib was given with chemotherapy (r = 0.005, P = 0.98). CONCLUSIONS: Treatment with chemotherapy led to increased amounts of COX-2 and PGE(2) in NSCLC. Cotreatment with celecoxib abrogated the increase in levels of PGE(2) but not COX-2 induced by chemotherapy. Importantly, these results clearly show that levels of a pharmacologic target (i.e., COX-2) can be affected by both the intrinsic molecular properties of a tumor and therapy. 相似文献
973.
Roland Schnell Markus Dietlein Jan Oliver Staak Peter Borchmann Klaus Schomaecker Thomas Fischer Wolfgang Eschner Hinrich Hansen Franck Morschhauser Harald Schicha Volker Diehl Andrew Raubitschek Andreas Engert 《Journal of clinical oncology》2005,23(21):4669-4678
PURPOSE: Hodgkin's lymphoma (HL) has been demonstrated to be a good target for immunotherapy since lymphocyte activation markers such as CD30 are expressed in high numbers on the malignant cells. Thus, we developed a new radioimmunoconjugate consisting of the murine anti-CD30 monoclonal antibody (MAb) Ki-4 labeled with iodine-131 ((131)I). PATIENTS AND METHODS: The biodistribution of (131)I-Ki-4 was assessed via dosimetry after preinfusion of 5 mg native Ki-4 followed by 250 to 300 MBq (131)I-labeled Ki-4. Whole-body scintigraphy was performed 1 hour, 24 hours, 48 hours, 72 hours, and 6 days after the infusion. Dosimetry was calculated using the programs NucliDose ICON-IDL (version 5.0.2; Siemens, Erlanger, Germany) and MIRDOSE (version 3.1; Oak Ridge National Laboratories; Oak Ridge, TN). The therapeutic dose was given on day 8 after preinfusion of unlabeled Ki-4. RESULTS: We treated 22 patients with relapsed or refractory CD30-positive HL. Preinfusion of 5 mg native Ki-4 was sufficient to bind the soluble CD30. Imaging demonstrated localization of involved areas measuring 5 cm in diameter or more in four patients and 2.5 cm in one patient. Patients received total body doses of 0.035 Gy to 0.99 Gy. Acute toxicity was mild with grade 1 fatigue in 19 of 22 assessable patients. Seven patients experienced grade 4 degrees hematotoxicity 4 to 8 weeks after treatment. Response included one complete remission, five partial remissions, and three minor responses. CONCLUSION: Treatment with (131)I-Ki-4 is effective but can be associated with severe hematotoxicity. 相似文献
974.
Andrew G Rundle Paolo Vineis Habibul Ahsan 《Cancer epidemiology, biomarkers & prevention》2005,14(8):1899-1907
Past discussions of the relative strengths of nested case-control and case-cohort designs have not fully considered cohorts with stored biological samples in which biomarker analyses are planned. Issues related to biomarker analyses can affect an investigator's choice of design and the conduct of these two designs. The key issues identified are effects of analytic batch, long-term storage, and freeze-thaw cycles on biomarkers. In comparison with the nested case-control design, the case-cohort design is less able to handle these challenges. Problems arise because most implementations of the case-cohort design do not allow for simultaneous evaluation of biomarkers in cases and reference group members, and there is no matching. By design, the nested case-control study controls for storage duration and the batching of biological samples from cases and controls is logistically simple. The allowance for matching also means that subjects can be matched on the number of freeze-thaw cycles experienced by the biological sample. However, the matching generates complex data sets that can be more difficult to analyze, and the costly biomarker data generated from the controls has few uses outside of testing the specific hypotheses of the study. In addition, because the same subject can serve as a control and a case, or multiple times as a control, biomarker analyses and sample batching can be more complex than initially anticipated. However, in total, of the two designs, the nested case-control study is better suited for studying biomarkers that can be influenced by analytic batch, long-term storage, and freeze-thaw cycles. 相似文献
975.
976.
Wendy R Parulekar Andrew G Day Jon A Ottaway Lois E Shepherd Maureen E Trudeau Vivien Bramwell Mark Levine Kathleen I Pritchard 《Journal of clinical oncology》2005,23(25):6002-6008
PURPOSE: To investigate the therapeutic impact of chemotherapy-induced amenorrhea in premenopausal patients with breast cancer. PATIENTS AND METHODS: We conducted a retrospective cohort study of a National Cancer Institute of Canada Clinical Trials Group phase III trial involving premenopausal patients randomized to receive cyclophosphamide, methotrexate, and fluorouracil (CMF), versus intensive cyclophosphamide, epirubicin, and fluorouracil (CEF). The objectives of our study were to describe the incidence of amenorrhea at 6 and 12 months post-random assignment and to determine the association of amenorrhea with relapse-free and overall survival. RESULTS: Data on 442 patients were used in our analyses. Despite the higher cumulative dose of cyclophosphamide in the CMF treatment arm, at 6 months post-random assignment, the rate of amenorrhea was higher in the CEF group (relative risk, 1.2; 95% CI, 1.0 to 1.3), with no difference at 12 months. In the receptor-positive subgroup, 6-month amenorrhea rates were not associated with prognosis. In contrast, amenorrhea at 12 months was significantly associated with relapse-free survival (hazard ratio, 0.51; 95% CI, 0.32 to 0.82; P = .005) and overall survival (hazard ratio, 0.40; 95% CI, 0.22 to 0.72; P = .002). CONCLUSION: Late chemotherapy-induced amenorrhea seems to be associated with improved outcome in patients with premenopausal, receptor-positive breast cancer. 相似文献
977.
Rushika M Perera Yoshitaka Narita Frank B Furnari Hui K Gan Carmel Murone Marika Ahlkvist Rodney B Luwor Antony W Burgess Elisabeth Stockert Achim A Jungbluth Lloyd J Old Webster K Cavenee Andrew M Scott Terrance G Johns 《Clinical cancer research》2005,11(17):6390-6399
Monoclonal antibody (mAb) 806 is a novel epidermal growth factor receptor (EGFR) antibody with significant antitumor activity that recognizes a mutant EGFR commonly expressed in glioma known as delta2-7 EGFR (de2-7 EGFR or EGFRvIII) and a subset of the wild-type (wt) EGFR found in cells that overexpress the receptor. We have used two human xenograft mouse models to examine the efficacy of mAb 806 in combination with mAb 528, a prototypical anti-EGFR antibody with similar specificity to cetuximab. Treatment of nude mice, bearing s.c. or i.c. tumor human xenografts expressing the wt or de2-7 EGFR, with mAbs 806 and 528 in combination resulted in additive and in some cases synergistic, antitumor activity. Interestingly, mAb 528 was also effective against xenografts expressing the ligand independent de2-7 EGFR when used as a single agent, showing that its antitumor activity is not merely mediated through inhibition of ligand binding. When used as single agents, neither mAbs 806 or 528 induced down-regulation of the de2-7 EGFR either in vitro or in vivo. In contrast, the combination of antibodies produced a rapid and dramatic decrease in the total cell surface de2-7 EGFR both in vitro and in xenografts. Consistent with this decrease in total cell surface de2-7 EGFR, we observed up-regulation of the cell cycle inhibitor p27(KIP1) and a decrease in tumor cell proliferation as measured by Ki-67 immunostaining when the antibodies were used in combination in vivo. Thus, mAb 806 can synergize with other EGFR-specific antibodies thereby providing a rationale for its translation into the clinic. 相似文献
978.
Danny Rischin Lester Peters Richard Fisher Andrew Macann Jim Denham Michael Poulsen Michael Jackson Lizbeth Kenny Michael Penniment June Corry David Lamb Bev McClure 《Journal of clinical oncology》2005,23(1):79-87
PURPOSE: To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost). RESULTS: Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms. CONCLUSION: Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial. 相似文献
979.
Steven P Treon Mark Hansen Andrew R Branagan Sigitas Verselis Christos Emmanouilides Eva Kimby Stanley R Frankel Nikolaos Touroutoglou Barry Turnbull Kenneth C Anderson David G Maloney Edward A Fox 《Journal of clinical oncology》2005,23(3):474-481
PURPOSE: Rituximab is an important therapeutic for Waldenstrom's macroglobulinemia (WM). Polymorphisms in FcgammaRIIIA (CD16) receptor expression modulate human immunoglobulin G1 binding and antibody-dependent cell-mediated cytotoxicity, and may therefore influence responses to rituximab. PATIENTS AND METHODS: Sequence analysis of the entire coding region of FcgammaRIIIA was undertaken in 58 patients with WM whose outcomes after rituximab were known. RESULTS: Variations in five codons of FcgammaRIIIA were identified. Two were commonly observed (FcgammaRIIIA-48 and FcgammaRIIIA-158) and predicted for amino acid polymorphisms at FcgammaRIIIA-48: leucine/leucine (L/L), leucine/arginine (L/R), and leucine/histidine (L/H). Polymorphisms at FcgammaRIIIA-158 were phenylalanine/phenylalanine (F/F), phenylalanine/valine (F/V), and valine/valine (V/V). A clear linkage between these polymorphisms was detected and all patients with FcgammaRIIIA-158F/F were always FcgammaRIIIA-48L/L, and patients with either FcgammaRIIIA-L/R or -L/H always expressed at least one valine at FcgammaRIIIA-158 (P < or = .001). The response trend was higher for patients with FcgammaRIIIA-48L/H (38.5%) versus -48L/R (25.0%) and LL (22.0%), and was significantly higher for patients with FcgammaRIIIA-158V/V (40.0%) and -V/F (35%) versus -158F/F (9.0%; P = .030). Responses for patients with FcgammaRIIIA-48L/L were higher when at least one valine was present at FcgammaRIIIA-158 (P = .057), thereby supporting a primary role for FcgammaRIIIA-158 polymorphisms in predicting rituximab responses. With a median follow-up of 13 months, no significant differences in the median time to progression and progression-free survival were observed when patients were grouped according to their FcgammaRIIIA-48 and -158 polymorphisms. CONCLUSION: The results of these studies therefore support a predictive role for FcgammaRIIIA-158 polymorphisms and responses to rituximab in WM. 相似文献
980.
Charles Butts Nevin Murray Andrew Maksymiuk Glenwood Goss Ernie Marshall Denis Soulières Yvon Cormier Peter Ellis Allan Price Ravinder Sawhney Mary Davis Janine Mansi Colum Smith Dimitrios Vergidis Paul Ellis Mary MacNeil Martin Palmer 《Journal of clinical oncology》2005,23(27):6674-6681
PURPOSE: To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. PATIENTS AND METHODS: Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 microg). Subsequent immunizations were administered at 6-week intervals. RESULTS: The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. CONCLUSION: L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed. 相似文献