***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Purpose : The purpose of this study was to determine the maximum tolerated dose , toxicity , and pharmacokinetics of BMS-247550 administered as a 1-h i.v . infusion every 3 weeks . Experimental Design : Patients with advanced solid malignancies were premedicated and treated with escalating doses of BMS-247550 . Blood sampling was performed to characterize the pharmacodynamics and pharmacokinetics of BMS-247550 . Results : Twenty-five patients were treated at six dose levels ranging from 7.4 to 59.2 mg/m2 . At 50 mg/m2 , 4 of 9 patients ( 44.4 % ) had dose-limiting toxicity ( neutropenia , abdominal pain/nausea ) . At 40 mg/m2 ( the recommended Phase II dose ) , 2 of 12 patients ( 16.7 % ) had dose-limiting neutropenia . Overall , the most common nonhematological toxicity was fatigue/generalized weakness ( grade 3–4 seen in 9.0 % of patients ) , followed by neurosensory deficits manifested as peripheral neuropathy and by gastrointestinal discomfort . At 40 mg/m2 , the incidence of grade 3 fatigue , abdominal pain , diarrhea , and neuropathy was 7.7 % . Grade 1–2 neuropathy was observed in all patients enrolled and treated at 40 mg/m2 . Two patients with paclitaxel-refractory ovarian cancer , one patient with taxane-naïve breast cancer , and another patient with docetaxel-refractory breast cancer had objective partial responses ( lasting 6.0 , 5.3 , 3.0 , and 4.5 months , respectively ) . The mean pharmacokinetic parameter values during course 1 for clearance , volume of distribution , and apparent terminal elimination half-life at the 40 mg/m2 ( recommended Phase II dose ) dose level were 21 liters/h/m2 , 826 liters/m2 , and 35 h ( excluding one outlier of 516 h ) , respectively . Values during course 1 and course 2 were similar . Conclusions : The recommended dose for Phase II evaluation of BMS-247550 is 40 mg/m2 , although more long-term observations are needed . BMS-247550 has advantages over taxanes in relation to drug resistance and warrants further study The epothilones are a novel class of microtubule‐stabilizing agents . Ixabepilone ( BMS‐247550 ; NSC 710428 ) is a semisynthetic analog of the natural product epothilone B. The authors conducted a Phase I study by administering ixabepilone to patients as a 1‐hour intravenous infusion daily for 3 consecutive days every 21 days PURPOSE Ixabepilone ( BMS-247550 ) is a microtubule-stabilizing epothilone B analog with activity in taxane-resistant metastatic breast cancer . The Gynecologic Oncology Group conducted a phase II evaluation of the efficacy and safety of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant primary ovarian or peritoneal carcinoma . PATIENTS AND METHODS Patients with measurable platinum- and taxane-resistant ovarian or peritoneal carcinoma , defined as progression during or within 6 months of one prior course of treatment with each agent , received intravenous ixabepilone 20 mg/m(2 ) administered over 1 hour on days 1 , 8 , and 15 of a 28-day cycle . Results Of 51 patients entered , 49 were eligible . The objective response rate was 14.3 % ( 95 % CI , 5.9 % to 27.2 % ) , with three complete and four partial responses . Twenty patients ( 40.8 % ) had stable disease , whereas sixteen ( 32.7 % ) had increasing disease . The median time to progression was 4.4 months ( 95 % CI , 0.8 to 32.6 + months ) ; median survival was 14.8 months ( 95 % CI , 0.8 to 50.0 ) months . Patients received a median of two treatment cycles ( range , 1 to 29 cycles ) , and 18.4 % of patients received > or = six cycles . Adverse effects included peripheral grade 2 ( 28.5 % ) and grade 3 ( 6.1 % ) neuropathy , grade s 3 to 4 neutropenia ( 20.4 % ) , grade 3 fatigue ( 14.3 % ) , grade 3 nausea/emesis ( 22 % ) , grade 3 diarrhea ( 10 % ) , and grade 3 mucositis ( 4 % ) . CONCLUSION Ixabepilone 20 mg/m(2 ) over 1 hour on days 1 , 8 , and 15 of a 28-day cycle demonstrates antitumor activity and acceptable safety in patients with platinum- and taxane-resistant recurrent or persistent ovarian or primary peritoneal carcinoma Purpose To establish the maximum tolerated dose ( MTD ) , dose-limiting toxicity ( DLT ) , safety and recommended Phase II dose of ixabepilone , administered weekly as an intravenous ( IV ) infusion to patients with solid tumors who have failed st and ard therapy . Method This was an open-label , single-arm , Phase I , dose-escalation study . Results The MTD of ixabepilone [ 30-min , weekly IV infusion on a 21-day schedule ( N = 33 ) ] was established at 25 mg/m2 . Grade 3 fatigue was the DLT in 2/4 patients treated at 30 mg/m2 . Ixabepilone was well tolerated at the MTD . Myelosuppression was rare , with no Grade 3/4 neutropenia . Due to the potential for cumulative neurotoxicity , the protocol was amended to a 1-h infusion , weekly for 3 weeks with a 1-week break . No DLT occurred at starting doses of 15 , 20 and 25 mg/m2 on this modified schedule ( N = 51 ) , although overall toxicity was less at 15 and 20 mg/m2 than 25 mg/m2 . Five patients ( 2 on the 30-min/21-day schedule and 3 on the 60-min/28-day schedule ) achieved durable objective partial responses across a variety of tumor types . Conclusions Ixabepilone had an acceptable safety profile at the MTD of 25 mg/m2 ( as a 30-min weekly infusion on a continuous 21-day schedule ) and at 20 mg/m2 ( as a 1-h weekly infusion on a modified 28-day schedule ) . The clinical activity and acceptable tolerability profile warrant further single- or combination-agent evaluation Purpose : Patupilone is a microtubule-targeting chemotherapeutic agent with clinical activity in a broad range of taxane-sensitive/resistant tumor types . The present phase Ib study examined the safety/tolerability and pharmacokinetics of patupilone in combination with carboplatin in patients with advanced solid tumors . Experimental Design : Patients with advanced cancer received patupilone via a 5- to 10-min i.v . infusion at doses of 3.6 to 6.0 mg/m2 q3w , immediately followed by carboplatin area under the curve ( AUC ) 5 or 6 mg/mL/min . Results : Of the 37 patients enrolled , the majority previously received taxanes ( 81 % ) and /or platinum-containing drugs ( 97.3 % ) . The maximum tolerated dose ( MTD ) of patupilone with carboplatin AUC 6 was 4.8 mg/m2 ; additional patients were enrolled to consoli date experience at this dose . Of the 22 patients who received the MTD , the most common nonhematologic adverse events were fatigue in six ( 27.3 % ) and diarrhea , nausea , vomiting , abdominal pain , and neuropathy in one each ( 4.5 % ; all grade 3 ) ; hematologic toxicities included two patients ( 9.1 % ) with grade 3 neutropenia . The pharmacokinetics of patupilone were similar to those in a previous study of patupilone monotherapy . Of the 26 patients with recurrent platinum-sensitive ovarian cancer , tumor response was assessable by response evaluation criteria in solid tumors in 17 ; 1 patient ( 6 % ) achieved a complete response , and 10 ( 59 % ) achieved a partial response . Conclusions : The combination of patupilone 4.8 mg/m2/carboplatin AUC 6 was well tolerated and showed antitumor activity similar to established regimens in patients with recurrent platinum-sensitive ovarian cancer . The optimal dose for this regimen is currently being further refined in phase II trials Background : Epothilones are a novel class of microtubule-stabilising agents , and sagopilone is a fully synthetic epothilone that has shown marked in vivo and in vitro pre clinical activity . Methods : This phase I , open-label study investigated the maximum tolerated dose ( MTD ) and dose-limiting toxicities ( DLTs ) of weekly sagopilone .  Twenty-three patients with malignancy resistant or refractory to st and ard treatment were enrolled into this study evaluating sagopilone doses from 0.6 to 7.0 mg m−2 . Results : The incidence of drug-related haematological adverse events ( AEs ) was low , with two grade 3 events observed . Nonhaematological AEs were generally mild and reversible ; increased γ-GT was the only grade 4 event and grade 3 events comprised peripheral neuropathy ( n=2 ) , diarrhoea ( n=1 ) and fatigue ( n=1 ) . Two grade 3 events were DLTs ( diarrhoea and peripheral neuropathy at 7.0 mg m−2 ) . The MTD of weekly sagopilone was therefore established as 5.3 mg m−2 . Stable disease was the best overall response ( n=3 ) . Microtubule bundle formation in peripheral blood mononuclear cells increased post-treatment , peaking after 1 h. Sagopilone disposition was similar across treatment courses and showed rapidly decreasing serum concentrations after infusion end and a long terminal disposition phase with no obvious accumulation in the serum , probably reflecting a fast uptake into tissues followed by a slow release . Conclusion : Weekly administration of sagopilone could represent an alternative to the 3-weekly administration currently evaluated in phase II trials BACKGROUND Ixabepilone is a semisynthetic epothilone B analogue that is active in taxane-resistant cell lines and has shown activity in patients with refractory breast and ovarian cancer . We carried out a phase I trial of ixabepilone plus pegylated liposomal doxorubicin ( PLD ) in patients with advanced taxane-pretreated ovarian and breast cancer . METHODS Patients with recurrent ovarian or breast carcinoma received PLD every 3 or 4 weeks plus five different dose schemas of ixabepilone in cohorts of three to six patients . RESULTS Thirty patients received a total of 142 treatment cycles of the PLD-ixabepilone combination . The recommended phase II dose and schedule of ixabepilone was 16 mg/m(2 ) on days 1 , 8 , and 15 plus PLD 30 mg/m(2 ) given on day 1 , repeated every 4 weeks . H and -foot syndrome and mucositis were dose limiting when both ixabepilone and PLD were given every 3 or 4 weeks . Objective responses were observed in 3 of 13 patients ( 23 % ) with breast cancer and 5 of 17 patients ( 29 % ) with ovarian cancer . CONCLUSION Ixabepilone may be safely combined with PLD , but tolerability is highly dependent upon the scheduling of both agents . This combination demonstrated efficacy in patients with breast and ovarian cancer and merits further evaluation in these setting PURPOSE The epothilones are a novel class of nontaxane microtubule-stabilizing agents . BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days . PATIENTS AND METHODS Twenty-one patients received  BMS-247550 without filgrastim in the first cycle . An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support .  Twenty-one of the 27 patients had received prior paclitaxel , docetaxel , or both .  RESULTS One hundred seven cycles were administered to 27 patients . The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days . Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support . Nonhematologic grade 3 toxicities included fatigue ( seven cycles ) , stomatitis ( two cycles ) , and anorexia ( one cycle ) . The mean terminal half 
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Despite the fact that epothilones have proven active in taxane-resistant setting s in pre clinical models , it is not yet clear from Phase II/III studies review ed here that their clinical activity is superior to that of taxanes .
Nevertheless , responses to epothilones have been observed in platinum-refractory/resistant ovarian cancer patients .
Moreover , despite the shared mechanism of action of epothilones , their clinical profile seems clearly different , with diarrhea being the most common dose-limiting toxicity encountered with patupilone , whereas neutropenia and sensory neuropathy are the most common toxic effects observed with the other epothilones .