Anti-cancer drugs
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Meta Analysis
Sorafenib improves the survival of patients with advanced hepatocellular carcinoma: a meta-analysis of randomized trials.
There is no effective systemic therapy for patients with advanced hepatocellular carcinoma (HCC) except liver transplantation. Sorafenib, a multikinase inhibitor, has been shown to significantly increase overall survival (OS) in a randomized, placebo-controlled, phase III trial of patients with HCC (SHARP). The aim of this study was to evaluate the effectiveness of sorafenib for advanced HCC by carrying out a meta-analysis of randomized controlled trials that compared sorafenib-based therapy with other agent-based therapy. ⋯ Sorafenib-based chemotherapy was also associated with a 79% prolongation of TPP (HR = 0.58, 95% CI = 0.49-0.69, P<0.001), and a 37.3% increase in OS (HR = 0.66, 95% CI = 0.55-0.78, P<0.001). Despite significant increases in the frequencies of hand-foot syndrome and diarrhea in patients receiving sorafenib-containing chemotherapy, no significant difference in other toxic events was observed. This meta-analysis suggests that sorafenib-based chemotherapy is superior to placebo-based chemotherapy in terms of TPP and OS without increase in severe toxic effects.
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Docetaxel, ifosfamide and cisplatin have proven activity in a broad range of solid tumours and interfere with different phases of the cell cycle. We performed a phase I study with the aim to determine the maximum tolerated dose (MTD) of docetaxel, ifosfamide and cisplatin in patients with solid tumours and to define the safety, dose-limiting toxicity (DLT) and the recommended dose and administration schedule of docetaxel, ifosfamide and cisplatin for further phase II testing. Docetaxel was given by 1-h infusion on day 1, followed by ifosfamide 1000 mg/m(2)/day as a continuous infusion for 5 days. ⋯ With a lower dose of docetaxel (60 mg/m(2)) both schedules A and B were feasible, although, overall, schedule A seemed to be better tolerated. On the basis of this phase I study, the recommended docetaxel, ifosfamide and cisplatin regimen is docetaxel (60 mg/m(2)) on day 1, ifosfamide (1000 mg/m(2)/day) on days 1-5 and cisplatin (75 mg/m(2)) given on day 5. It is associated with substantial haematological toxicity, but this is feasible provided prophylactic antibiotics are used.
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Chemotherapy used to be the only available option to fight advanced nonsmall cell lung cancer. Platinum-based medication combined with taxanes, vinca alkaloids, and antimetabolites improved patient survival rates. Unfortunately, neoplasmatic diseases remain a global killer because chemotherapy benefits have reached a plateau and most patients are diagnosed at the metastatic stage. ⋯ Hence, numerous multidynamic agents have appeared in the hope that they might help fight nonsmall cell lung cancer. However, no group of patients who will hopefully gain maximum benefit from such interventions has been clearly identified yet. This paper presents current evidence with regard to such novel agents and angiogenesis and epidermal growth factor inhibitors.
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Clinical Trial
Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy.
Patients with large cell neuroendocrine carcinoma (LCNEC) of the lung are considered to have poor prognosis. However, the benefit of adjuvant chemotherapy for these patients has not been established. In this study, we retrospectively evaluated the efficacy of perioperative chemotherapy for patients with completely resected LCNEC in a single-center setting. ⋯ In conclusion, perioperative chemotherapy will be needed to improve survival in patients with LCNEC. As the population of LCNEC is small, it has been difficult to conduct randomized controlled trials to show the survival benefit of adjuvant chemotherapy. This should be, therefore, evaluated further in prospective multi-institutional phase II trials.
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Previously, we synthesized a series of hydrazide class of compounds and examined their cytotoxicity in a number of cancer cell lines. Among these analogues, SC144 exhibited potent cytotoxicity against a panel of drug-sensitive and drug-resistant cancer cell lines. To further explore its therapeutic potentials in the combination settings, we evaluated the synergy between SC144 and selected conventional chemotherapeutic agents in in-vitro cancer cell models. ⋯ In an MDA-MB-435 mouse xenograft model, coadministration of SC144 and paclitaxel delayed tumor growth in an SC144 dose-dependent manner. Evaluation of the pharmacokinetics of SC144 revealed that intraperitoneal administration of SC144 showed a two-compartmental pharmacokinetics elimination profile that was not observed in the oral dosing. In summary, these studies further validate SC144 as a novel anticancer agent and provide insights for developing combination therapies for both drug-sensitive and drug-resistant cancers.