Showing papers by "Amit M. Oza published in 2005"
TL;DR: 2004 consensus statements on the management of ovarian cancer : final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC).
422 citations
TL;DR: The significant antitumor activity combined with a mild toxicity profile seen in this study argue that GemCap chemotherapy may benefit patients with advanced biliary cancer.
Abstract: Purpose Biliary cancer has a poor prognosis, and chemotherapy has had little impact. The objectives of this trial were to determine the response rate, time to disease progression, survival, and safety profile of the combination of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer. Patients and Methods Eligible patients had pathologically proven, locally advanced or metastatic adenocarcinoma arising from the intra- and extrahepatic bile ducts or gallbladder with no prior chemotherapy. Patients were treated on a 3-week cycle consisting of capecitabine at 650 mg/m2 orally twice a day for 14 days and gemcitabine at a fixed dose of 1,000 mg/m2 intravenously over 30 minutes on days 1 and 8. Results Forty-five patients were enrolled between July 2001 and January 2004. Fifty-three percent of patients had cholangiocarcinoma, 47% had gallbladder cancer, and 89% had metastatic disease. The overall objective response rate was 31%, with an additional 42% of patients with stable disease, fo...
291 citations
TL;DR: Results indicate that further clinical investigation of BAY 43--9006 is warranted, and suggest it could be a promising future therapy for patients with cancer.
290 citations
TL;DR: There appears to be no association between baseline erbB expression and disease stability in unscreened patients with advanced ovarian cancer, and CI-1033 had a more favorable adverse events profile than at 200 mg/d.
Abstract: Purpose To evaluate the antitumor activity and toxicity of two doses of CI-1033 in patients with platinum-refractory or recurrent ovarian cancer, and to determine baseline expression of epidermal growth factor receptor in tumor cells. Patients and Methods This phase II, open-label clinical trial evaluated CI-1033 in patients with ovarian cancer who failed prior platinum-based therapy. Two oral doses of CI-1033 were evaluated—a 50-mg and a 200-mg oral dose administered daily for 21 days in a 28-day cycle. Patients were evaluated for tumor response and toxicity; in addition, archival baseline tumor samples were analyzed by immunohistochemistry for erbB1 to erbB4 status. Results One hundred five eligible patients were treated. Baseline demographic characteristics were balanced in this heavily pretreated patient population. The median number of prior chemotherapy regimens received was four. The most commonly encountered drug-related adverse events for both dose arms were gastrointestinal (diarrhea, nausea, st...
110 citations
TL;DR: Patupilone is well tolerated when administered at a dose of 2.5 mg/m2, in patients with advanced solid tumors, and the partial responses in patients previously treated with taxanes is consistent with promising preclinical results.
Abstract: Purpose To evaluate the safety and maximum-tolerated dose (MTD) of weekly patupilone, a natural epothilone B, in patients with advanced solid tumors. Patients and Methods Patients were treated with patupilone (0.3 to 3.6 mg/m2) for 6 weeks on/3 weeks off or 3 weeks on/1 week off. Dose-limiting toxicities (DLTs), MTD, and pharmacokinetics were determined for each schedule of administration. Results Ninety-one patients were enrolled. The most common tumor types included ovarian, breast, and colon cancers. Doses of patupilone less than 2.5 mg/m2 using either the 6 weeks on/3 weeks off or the 3 weeks on/1 week off schedule were tolerated well. At higher doses, DLTs were observed using both dosing schedules, with diarrhea the most common DLT. The MTD for both treatment schedules was 2.5 mg/m2. After a short infusion, patupilone blood concentrations declined in a multiphasic manner with a terminal half-life of 4 days. Drug clearance was nonrenal and was not related to body-surface area. Over the dose range eval...
98 citations
TL;DR: There was a significant increase in the expression of HIF-1α relative to its transcriptional target CAIX following bortezomib, and a similar effect was also observed in a companion study using a human tumor xenograft model.
Abstract: Purpose: To evaluate the effects of the proteasome inhibitor bortezomib on tumor growth in patients with advanced colorectal cancer, and to explore the relationship between correlative studies and clinical outcome.
Design: Bortezomib (1.3 mg/m2) was administered i.v. on days 1, 4, 8, and 11 of a 21-day cycle. Tumor response was assessed after every two cycles. Tumor biopsies were done prior to treatment and on day 9 of the first treatment cycle. Biopsies were examined for Ser32/36-IκB, Ser276-nuclear factor κB (NFκB), hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase IX (CAIX), p53, and microvessel density using immunohistochemistry.
Results: Nineteen patients received 42 cycles (range 1-4) of bortezomib. No objective response was seen; three patients had stable disease at cycle 2, two patients had progressive disease after cycle 1, and 11 patients had progressive disease at cycle 2. Of the three patients with stable disease, one had progressive disease after cycle 4, and two were withdrawn due to toxicity. The median time to progression was 5.1 weeks (95% confidence interval, 5.1-11.1 weeks). There was a significant increase in the expression of HIF-1α relative to its transcriptional target CAIX following bortezomib, and a similar effect was also observed in a companion study using a human tumor xenograft model. Expression of p53, Ser276-NFκB, and Ser32/36-IκB was unchanged.
Conclusion: Single agent bortezomib is inactive in metastatic colorectal cancer. Using this regimen, there was no detectable effect on NFκB, but a significant accumulation of HIF-1α was seen relative to CAIX. This suggests that proteasome inhibition alters the response to tumor hypoxia, and further investigation of this effect is indicated.
94 citations
TL;DR: Bev is a recombinant humanized anti-VEGF monoclonal antibody that inhibits the growth of a number of human cancers, including ovarian cancer, and low dose chronic chemotherapy (metrono...
Abstract: 5000 Background: Bev is a recombinant humanized anti-VEGF monoclonal antibody that inhibits the growth of a number of human cancers, including ovarian cancer. Low dose chronic chemotherapy (metrono...
68 citations
TL;DR: This phase I/II study is investigating the safety and efficacy of patupilone in pts with advanced ovarian cancer who had failed to respond to or had relapsed within 6 months of first-line platinum therapy.
Abstract: 5056 Background: Pts with newly diagnosed advanced ovarian cancer generally receive platinum plus taxane therapy. For pts who do not respond or relapse within 6 months, outlook remains poor. Patupilone, a natural epothilone, is a microtubule-targeting cytotoxic that has demonstrated clinical activity in taxane-sensitive and -resistant tumors. In a phase I/II study, we are investigating the safety and efficacy of patupilone in pts with advanced ovarian cancer who had failed to respond to or had relapsed within 6 months of first-line platinum therapy. Methods: Pts receive patupilone at a starting dose of 6.5 mg/m2 via 10- to 20-min IV infusion once every 3 wk (q3w) with proactive diarrhea management. Results: To date, 31 pts have been enrolled in 9 cohorts receiving 6.5 (n = 3), 7.0 (n = 3), 7.5 (n = 3), 8.0 (n = 6), 8.5 (n = 3), 9.0 (n = 6), 9.5 (n = 3), 10.0 (n = 3), and 10.5 (n = 1) mg/m2 patupilone. Currently, 29 pts are eligible for assessment; 90% had received prior taxane therapy. DLTs were not repor...
34 citations
TL;DR: The maximum tolerated dose (MTD) of zosuquidar in combination with vinorelbine was 300 mg/m2 orally every 12 h for 3 days weekly for 3–weeks every 28 days, and Vinore lbine pharmacokinetic studies showed reduced clearance when given with zosUquidr.
Abstract: Zosuquidar (LY335979) is an oral P-glycoprotein modulator. This phase I study was designed to determine the maximum tolerated dose (MTD) of zosuquidar in combination with vinorelbine. The effects of zosuquidar on vinorelbine pharmacokinetics were also examined. Patients with advanced solid tumours were treated with escalating doses of zosuquidar administered every 8–12 h on days 7–9 and 14–16 during cycle 1 then days 0–2, 7–9, and 14–16 from cycle 2 onwards, with vinorelbine 22.5–30 mg/m2
IV on days 1, 8 and 15 every 28 days. Of 21 patients registered, 19 were treated at four dose levels (zosuquidar 100–300 mg/m2). Two patients had prolonged and febrile neutropenia at the second dose level resulting in a reduction of the dose of vinorelbine in subsequent dose levels. There was another patient with dose-limiting febrile neutropenia at dose level four which resulted in the expansion of the dose level three. Eight patients had stable disease and no objective responses were seen. Vinorelbine pharmacokinetic studies showed reduced clearance when given with zosuquidar. The MTD was zosuquidar 300 mg/m2 orally every 12 h for 3 days weekly for 3 weeks with vinorelbine 22.5 mg/m2 IV weekly for 3 weeks every 28 days. Zosuquidar may inhibit vinorelbine clearance to a modest degree.
34 citations
TL;DR: Conformal radiotherapy may improve acute toxicity (25% grade 3 or greater toxicity as compared with 41% reported in INT-0116) and survival is comparable to that achieved in the INT- 0116 treatment arm (approximately 60% at 2 years).
27 citations
TL;DR: This phase I, open-label, dose-escalation study assesses the tolerability and toxicity profile of ≥ 2 doses of HGS-ETR1 administered IV in patients with advanced solid tumors or NHL and evaluates the pharmacokinetic (PK) profile and immunogenicity of H GS- ETR1.
Abstract: 3052 Introduction: HGS-ETR1 (TRM-1) is a fully human monoclonal antibody that is agonistic to the R1 (TRAIL-R1 or DR4) receptors for TRAIL that are expressed on the surface of multiple cancer cell ...
TL;DR: The combination of carboplatin and PLD is well tolerated with sufficient activity to justify additional evaluation in clinical trials and might be suited to the addition of a taxane.
Abstract: The results of a multicenter phase II study investigating carboplatin and pegylated liposomal doxorubicin (PLD) in patients with recurrent/metastatic uterine and cervical malignancies (UCM) are presented here. Fifty-three subjects with measurable, untreated, advanced UCM were enrolled. Fifty-one were evaluable for response. Prior combined-modality treatment was permitted if a component of primary therapy. Patients received carboplatin AUC = 5 with PLD 35 mg/m2 intravenously once every 4 weeks. Overall response rate was 33% (35% stable disease). Overall survival (OS) at six months was 86% (95% CI 76%–96%). Six-month progression-free survival (PFS) was 43% (95% CI 30%–57%). Median PFS was 22.9 weeks (range 16.0–35.3) and median OS was 49.1 weeks (range 41.4–75.1). The most frequent grade 3-4 nonhematological adverse events were: abdominal pain (n = 7), fatigue (4), vomiting (4), nausea (3), and shortness of breath (3). There was 1 report of grade 3 hand-foot syndrome and none of grade 4. Twelve patients had first infusion reactions with only 1 discontinuing treatment. Grade 3-4 neutropenia occurred in 26/230 cycles (11.3%). There were no treatment-related deaths. The combination of carboplatin and PLD is well tolerated with sufficient activity to justify additional evaluation in clinical trials and might be suited to the addition of a taxane.
TL;DR: This manuscript will first summarize those specific questions that were generated through this OCCC which require further action before the next Conference and seek to collate those new questions that emanated from this Conference and may be considered for future consensus statements.
TL;DR: Patupilone is a natural epothilone, which is a microtubule-targeting cytotoxic that has demonstrated clinical activity in taxane-sensitive and resistant tumors and produces synergistic in this paper.
Abstract: 5087 Background: Patupilone, a natural epothilone, is a microtubule-targeting cytotoxic that has demonstrated clinical activity in taxane-sensitive and -resistant tumors and produces synergistic in...
TL;DR: Integration of new or experimental treatment options and new approaches to clinical trials are integrated into existing clinical trials.
TL;DR: Recurrent and metastatic cervical cancer is not curable with conventional therapy, and the median survival is only about 9 months, but high objective response rates have been reported.
Abstract: 5103 Background: Recurrent and metastatic cervical cancer is not curable with conventional therapy, and the median survival is only about 9 months. High objective response rates have been reported ...
TL;DR: Rational selection of therapy in AOC requires molecular and prognostic profiling and clinical and molecular markers from patients who participated in a AOC trial were analyzed.
Abstract: 5005 Background: Rational selection of therapy in AOC requires molecular and prognostic profiling. We analyzed clinical (clin) and molecular (mol) markers from patients (pts) who participated in a ...
01 Jan 2005
TL;DR: Patients with normal or premalignant lesions who are at high risk of developing a malignancy are best employed in chemopreventive strategies, which prevent or reverse the initiation, promotion, or progression of carcinogenesis.
Abstract: Chemoprevention refers to the use of micronutrients or pharmaceutical agents to prevent or delay the development of cancer in healthy populations. Agents employed in chemopreventive trials should prevent or reverse the initiation, promotion, or progression processes involved with carcinogenesis. Chemoprevention strategies would therefore be best employed in patients with normal or premalignant lesions who are at high risk of developing a malignancy.