We report a rare case of extrapulmonary small cell carcinoma arising in the palatine tonsil treated by combined chemotherapy with irinotecan/cisplatin following irradiation therapy. This chemotherapy regimen was recently found to be effective for small cell lung carcinoma. Our case is the first report of combined irinotecan/cisplatin chemotherapy to treat extrapulmonary small cell carcinoma of ...

Pharmacogenetic research indicates a relationship between a polymorphism in the gene encoding uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and irinotecan inactivation, in that degradation of SN-38, the active metabolite of irinotecan, correlates inversely with the number of TA repeats in the TATA element of the UGT1A1 promoter region. Individuals who are homozygous for the UGT1A1*28...

A major challenge in the clinical use of cytotoxic chemotherapeutics is maximizing efficacy in tumors while sparing normal tissue. Irinotecan is used for colorectal cancer treatment but the extent of its use is limited by toxic side effects. Liposomal delivery systems offer tools to modify pharmacokinetic and safety profiles of cytotoxic drugs. In this study, we defined parameters that maximize...

PURPOSE This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. METHODS To test if an irinotecan signature and a SN-38 signature could identify patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based o...

PURPOSE Activating mutation of the KRAS oncogene is an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, KRAS mutation as a prognostic factor of survival outcome remains controversial in CRC, independent of anti-EGFR therapies. MATERIALS AND METHODS We conducted a retrospective analysis of 103 CRC pat...

Locally advanced non small-cell lung cancer (NSCLC) represents 30%-40% of all pulmonary malignancies. Despite the fact that the disease is confined to the chest, most patients will eventually succumb to their dis-ease. Therefore, the management of NSCLC is undergoing rapid evolution with hope of improving overall survival. The arrival of a new generation of chemotherapeutic agents, including th...

PURPOSE To determine the pharmacokinetics and the antitumor activity in pediatric cancer models of MM-398, a nanoliposomal irinotecan (nal-IRI). EXPERIMENTAL DESIGN Mouse plasma and tissue pharmacokinetics of nal-IRI and the current clinical formulation of irinotecan were characterized. In vivo activity of irinotecan and nal-IRI was compared in xenograft models (3 each in nu/nu mice) of Ewing...

Purpose: To determine the pharmacokinetics and the antitumor activity in pediatric cancer models of MM-398, a nanoliposomal irinotecan (nal-IRI). Experimental Design: Mouse plasma and tissue pharmacokinetics of nal-IRI and the current clinical formulation of irinotecan were characterized. In vivo activity of irinotecan and nal-IRI was compared in xenograft models (3 each in nu/nu mice) of Ewing...

BACKGROUND We have investigated the efficacy, safety and quality of life profiles of three therapeutic combinations [irinotecan + leucovorin (LV)/5-fluorouracil (5-FU), oxaliplatin + LV/5-FU and irinotecan +oxaliplatin] in patients with metastatic colorectal cancer after failure of a 5-FU-based regimen, or whose disease had progressed within 6 months of the end of treatment. PATIENTS AND METH...

OBJECTIVE The treatment of lupus nephritis is still an unmet medical need requiring new therapeutic approaches. Our group found recently that irinotecan, an inhibitor of topoisomerase I (topo I), reversed proteinuria and prolonged survival in mice with advanced lupus nephritis. While irinotecan is known to stabilize the complex of topo I and DNA, the enzyme tyrosyl-DNA phosphodiesterase 1 (TDP-...