Anti-cancer drugs
-
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.
-
Gastrointestinal stromal tumors (GIST) are the most common malignant mesenchymal tumors of the gastrointestinal tract. The principal treatment modality for primary GIST is surgery whereas for metastatic GIST, imatinib has an established role. In patients with locally advanced and metastatic GIST, the role of surgery in the imatinib era is still unclear. ⋯ In conclusion, preoperative imatinib treatment in patients with locally advanced GIST resulted in a decrease of tumor load in most patients, enabling complete surgical resection. For patients with metastatic GIST, the role of surgery remains less clear. Loss or decrease of CD117 expression in the resected specimen after imatinib treatment may be associated with disease recurrence.
-
Pegylated liposomal doxorubicin (PLD) is active in recurrent platinum-refractory ovarian and peritoneal cancer as demonstrated in a prospective-randomized trial. Dose-limiting toxicity in the US Food and Drug Administration-approved application schedule of PLD (50 mg/m2 every 4 weeks) was serious palmar-plantar erythrodysaesthesia (PPE). This phase II trial was aimed at reduction of the frequency of serious PPE without loss of efficacy by modifying both the application schedule and the total dose of PLD administered as palliative single-agent chemotherapy. ⋯ No grade 4 toxicity occurred. PLD 20 mg/m2 biweekly is highly active in patients with recurrent platinum-refractory ovarian and peritoneal cancer. The frequency of grade 3 and grade 4 PPE was remarkably reduced in this trial, as compared with the frequency of serious PPE observed in patients who were administered the dose schedule of 50 mg/m2 every 4 weeks.
-
Comparative Study
Intergroup Exemestane Study mature analysis: overall survival data.
The findings of the Intergroup Exemestane Study (IES) challenge the standard adjuvant endocrine therapy consisting of 5 years of tamoxifen therapy in women with oestrogen receptor-positive breast cancer. The IES study confirmed that switching to an aromatase inhibitor (AI) such as exemestane after 2-3 years of tamoxifen therapy resulted in improved survival relative to women remaining on 5 years of tamoxifen therapy. Data from IES concur with the findings of other studies with AIs that support the rationale of switching from tamoxifen to an AI after 2-3 years of tamoxifen in postmenopausal women who remain disease-free.