Investigational new drugs
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Investigational new drugs · Aug 2013
Meta AnalysisRisk of hand-foot skin reaction with the novel multikinase inhibitor regorafenib: a meta-analysis.
Regorafenib is a novel receptor tyrosine kinase inhibitor approved for use in metastatic colorectal cancer (mCRC) and locally advanced gastrointestinal stromal tumors (GISTs). The drug targets multiple receptors, including VEGF-R1/-R2/-R3, TIE-2, FGFR-1, PDGFR-α/β, KIT, RET, RAF, p38 MAPK. Adverse events include asthenia, hypertension, diarrhea, and hand-foot skin reaction (HFSR), with the latter representing one of the most clinically significant untoward events. The incidence and risk of HFSR with regorafenib have not been systematically investigated. ⋯ The incidence and risk of development of HFSR with regorafenib is high, and may vary significantly with tumor type. Knowledge of this is important for patient counseling and clinical trial development, to ensure adherence and maximize clinical outcomes.
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Investigational new drugs · Jun 2013
A phase I pharmacokinetic study of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer.
Matuzumab is a humanized IgG1 EGFR monoclonal antibody. This phase I study investigated the tolerability, safety and pharmacokinetics (PK) of matuzumab in combination with paclitaxel in patients with EGFR-expressing advanced non-small cell lung cancer (NSCLC). Six dose levels/schedules of matuzumab were explored in combination with paclitaxel. ⋯ Tumor growth control was seen in 15/44 (34 %) patients, including 5/9 (56 %) at the 800 mg weekly dose level. Matuzumab combined with paclitaxel was generally well tolerated in patients with advanced NSCLC. There was some evidence of anticancer activity in relation to the matuzumab 800 mg weekly dose.
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Investigational new drugs · Jun 2013
Phase I study of matuzumab in combination with 5-fluorouracil, leucovorin and cisplatin (PLF) in patients with advanced gastric and esophagogastric adenocarcinomas.
To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanced gastric and esophagogastric adenocarcinomas. ⋯ Matuzumab, in combination with PLF, demonstrated an acceptable safety profile with modest anti-tumor activity.
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Investigational new drugs · Jun 2013
Phase I study of PM00104 (Zalypsis®) administered as a 1-hour weekly infusion resting every fourth week in patients with advanced solid tumors.
PM00104 (Zalypsis®) is a new synthetic alkaloid with potent cytotoxic activity against tumor cell lines. This phase I clinical trial determined the maximal tolerated dose (MTD) and recommended dose (RD) for phase II trials of PM00104 administered as a 1-hour intravenous (i.v.) infusion weekly for three consecutive weeks resting every fourth week (d1,8,15 q4wk). Forty-nine patients with advanced solid malignancies received PM00104 following a toxicity-guided, accelerated, dose-escalation design. ⋯ Main pharmacokinetic parameters increased linearly with dose. Disease stabilization lasting ≥ 3 months was found in 4 patients with cervical carcinoma, colorectal adenocarcinoma, lachrymal adenoid carcinoma, and bladder carcinoma (n=1 each). In conclusion, PM00104 2.0 mg/m(2) 1-hour, d1,8,15 q4wk showed a positive risk-benefit ratio, which has supported its further evaluation in three ongoing phase II clinical trials.
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Investigational new drugs · Aug 2012
Multicenter StudyBiweekly cetuximab plus irinotecan as second-line chemotherapy for patients with irinotecan-refractory and KRAS wild-type metastatic colorectal cancer according to epidermal growth factor receptor expression status.
Cetuximab plus irinotecan has been shown to be effective in metastatic colorectal cancer (mCRC) patients with wild-type (WT) KRAS and positive EGFR expressions (EGFR+). Retrospective analysis revealed that the efficacy of cetuximab was similar in mCRC patients negative (EGFR-) and positive for EGFR. However, the efficacy of cetuximab has not been assessed prospectively in EGFR- mCRC patients. ⋯ Biweekly cetuximab plus irinotecan as second-line treatment showed significant anti-tumor activity in patients with irinotecan-refractory mCRC and WT-KRAS regardless of EGFR expression status.