Phase I trial of the novel taxane BMS-184476 administered in combination with carboplatin every 21 days

Bilenker, Joshua H.; Stevenson, James P.; Gallagher, Maryann; Vaughn, David J.; Cohen, Marvin B.; O’Dwyer, Peter J.

doi:10.1038/sj.bjc.6601885

Cited by 7 publications

(5 citation statements)

References 7 publications

(7 reference statements)

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“…Another candidate for further trials might be the second novel paclitaxel derivative, BMS-184476, a 7-methylthiomethyl ether of paclitaxel, which was also investigated in single-agent phase I trials (Plummer et al, 2002) and in combination with cisplatin (Sun et al, 2003) and carboplatin (Bilenker et al, 2004). Similar to our results, neutropenia and diarrhoea were the DLTs for BMS-184476 in combination with cisplatin; other toxicities were comparable with paclitaxel/cisplatin.…”

Section: Discussionsupporting

confidence: 85%

A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours

et al. 2005

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This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m À2 DL), combined with cisplatin (standard dose 75 mg m À2 ). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m À2 DL; at the 110 mg m À2 DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m À2 , but not through the 150 mg m À2 DL. The mean7SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317760 ml min À1 m À2 , 258796 l m À2 and 30.877.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m À2 (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m À2 .

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Section: Discussionsupporting

confidence: 85%

A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours

et al. 2005

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“…These include taxane analogs DJ-927 (phase I/Il)[57]–[59] and ortataxel (phase II)[60],[61], as well as BMS-184476 (phase II)[62]–[64] and RPR 109881A (phase I)[65]–[67], which were purported to have a broad spectrum of activity both in sensitive and resistant tumor cell lines. Nab-paclitaxel is a novel clinical entity incorporating paclitaxel into an albumin nanoparticle, leading to increased intratumoral concentration and showing with superior response rate, longer time to tumor progression, and prolonged survival as second-line therapy in patients with gynecologic cancers[68],[69].…”

Section: Cancer Nanomedicine For Overcoming Drug Efflux-mediated Resimentioning

confidence: 99%

Overcoming drug efflux-based multidrug resistance in cancer with nanotechnology

Xue¹,

Liang²

2012

Chin J Cancer

143

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Multidrug resistance (MDR), which significantly decreases the efficacy of anticancer drugs and causes tumor recurrence, has been a major challenge in clinical cancer treatment with chemotherapeutic drugs for decades. Several mechanisms of overcoming drug resistance have been postulated. Well known P-glycoprotein (P-gp) and other drug efflux transporters are considered to be critical in pumping anticancer drugs out of cells and causing chemotherapy failure. Innovative theranostic (therapeutic and diagnostic) strategies with nanoparticles are rapidly evolving and are anticipated to offer opportunities to overcome these limits. In this review, we discuss the mechanisms of drug efflux-mediated resistance and the application of multiple nanoparticle-based platforms to overcome chemoresistance and improve therapeutic outcome.

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“…BMS-184476 was studied in combination with carboplatin and was well tolerated at a dose of 50/AUC 6 and showed evidence of antitumor activity in a heavily pretreated patient population. DLT at 60/AUC 6 was neutropenia 56. Weekly schedules of BMS-184476 were also evaluated with BMS-184476 IV on days 1, 8, and 15 without premedication, the maximum administered dose was 60 mg/m 2 /week, and the MTD was 50 mg/m 2 /week with neutropenia as the main toxicity and DLT.…”

Section: Bms-184476mentioning

confidence: 99%

“…Other nonhematological toxicities, such as nausea and vomiting, myalgia and arthralgia, diarrhea, and mucositis, were uncommon. In a Phase II study of BMS-184476 and carboplatin, neutropenia was the DLT 56. With a weekly dosage on days 1, 8, 15, for an every 28-day schedule, neutropenia, and diarrhea were the main toxicities; other toxicities included vomiting, cumulative fatigue, and loss of appetite.…”

Section: Bms-184476mentioning

confidence: 99%

Update on taxane development: new analogs and new formulations

Yared¹,

Tkaczuk²

2012

DDDT

122

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The taxanes (paclitaxel and docetaxel) represent an important class of antineoplastic agents that interfere with microtubule function leading to altered mitosis and cellular death. Paclitaxel (Taxol®) was originally extracted from a yew tree (Taxus spp., Taxaceae) a small slow-growing evergreen, coniferous tree. Due to the initial scarcity of paclitaxel, docetaxel (Taxotere®) a semisynthetic analog of paclitaxel produced from the needles of European yew tree, Taxus baccata was developed. Docetaxel differs from paclitaxel in two positions in its chemical structure and this small alteration makes it more water soluble. Today, paclitaxel and docetaxel are widely prescribed antineoplastic agents for a broad range of malignancies including lung cancer, breast cancer, prostate cancer, Kaposi’s sarcoma, squamous cell carcinoma of the head and neck, gastric cancer, esophageal cancer, bladder cancer, and other carcinomas. Although very active clinically, paclitaxel and docetaxel have several clinical problems including poor drug solubility, serious dose-limiting toxicities such as myelosuppression, peripheral sensory neuropathy, allergic reactions, and eventual development of drug resistance. A number of these side effects have been associated with the solvents used for dilution of these antineoplastic agents: Cremophor EL for paclitaxel and polysorbate 80 for docetaxel. In addition, reports have linked these solvents to the alterations in paclitaxel and docetaxel pharmacokinetic profiles. In this review, we provide preclinical and clinical data on several novel taxanes formulations and analogs which are currently US Food and Drug Administration (FDA)-approved or in clinical development in various solid tumor malignancies. Of the new taxanes nab-paclitaxel and cabazitaxel have enjoyed clinical success and are FDA-approved; while many of the other compounds described in this review are unlikely to be further developed for clinical use in daily practice. Furthermore, the successful clinical emergence of novel nontaxane microtubule-targeting chemotherapy agents such as epothilones and eribulin is liable to further restrict the development of novel taxanes.

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Phase I trial of the novel taxane BMS-184476 administered in combination with carboplatin every 21 days

Cited by 7 publications

References 7 publications

A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours

A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours

Overcoming drug efflux-based multidrug resistance in cancer with nanotechnology

Update on taxane development: new analogs and new formulations

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