From Yahoo Blogger...FOLPI efficacy seems comparable to FOLFOX. It's neuropathy sparing (good). The negatives are higher incidence of neutropenia and thrombocytopenia, but those are considered manageable. So would doctors and patients prefer FOLFOX or FOLPI? (Obviously, if patients develop resistance to oxaliplatin, picoplatin would be viable. But as a front line treatment, which would be preferred?) http://www.abstract.asco.org/AbstView_65... Randomized phase II study of picoplatin in combination with 5-fluorouracil and leucovorin (FOLPI) as a neuropathy-sparing alternative to modified FOLFOX-6 as first-line therapy for colorectal cancer (CRC). Author(s): R. Earhart, S. Cheporov, O. Gladkov, M. Biakhov, H. Breitz, R. De Jager; Poniard Pharmaceuticals, South San Francisco, CA; Regional Clinical Oncology Hospital, Yaroslavl, Russian Federation; Chelyabinsk Regional Oncology Center, Chelyabinsk, Russian Federation; Semashko Central Clinical Hospital #2 , Moscow, Russian Federation Abstract: Background: Picoplatin (Pico) was designed to overcome platinum resistance and has the potential for improved safety compared to other platinum agents. FOLFOX (5-FU, LV, oxaliplatin [oxali]) treatment for advanced CRC has dose-limiting oxali- related neurotoxicity. The incidence of grade (G) 3-4 neurotoxicity with single-agent Pico across studies was

Updated remission duration and survival results of single-agent clofarabine in previously untreated older adult patients with acute myelogenous leukemia (AML) unlikely to benefit from standard induction chemotherapy due to unfavorable baseline risk factor(s). Sub-category: Leukemia Category: Leukemia, Myelodysplasia, and Transplantation Meeting: 2009 ASCO Annual Meeting Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 7062) Abstract No: 7062 Attend this session at the ASCO Annual Meeting! Session: Leukemia, Myelodysplasia, and Transplantation Type: General Poster Session Time: Saturday May 30, 8:00 AM to 12:00 PM Location: Level 2, West Hall C Personalize your Annual Meeting experience with a suggested or customized itinerary! Author(s): H. P. Erba, H. M. Kantarjian, D. F. Claxton, M. Arellano, R. M. Lyons, T. J. Kovacsovics, J. Gabrilove, S. Eckert, S. Faderl; University of Michigan Health System, Ann Arbor, MI; M. D. Anderson Cancer Center, Houston, TX; Penn State's Milton S. Hershey Medical Center, Hershey, PA; Emory University, Atlanta, GA; Cancer Care Centers South Texas/US Oncology, San Antonio, TX; Center for Hematological Malignancies OHSU, Portland, OR; Mount Sinai School of Medicine, New York, NY; Genzyme, San Antonio, TX; Department of Leukemia, M. D. Anderson Cancer Center, Houston, TX Abstract: Background: The CLASSIC II trial has previously reported an independently confirmed overall remission rate of 46% (38% CR and 8% CRp) and 30- and 60-day mortality rates of 9.8% and 16.1%, respectively (Blood 112: 558, 2008). We now report updated duration of remission (DOR), disease-free survival (DFS), and overall survival (OS). Methods: Single arm, multi-center, phase II, open-label, 2-stage study of patients with untreated AML, ≥60 years old, and at least one adverse prognostic factor: age ≥70 years, antecedent hematologic disorder (AHD), PS = 2, and/or intermediate/unfavorable risk karyotype. Clofarabine (CLO) administered days 1-5 at 30 mg/m2 during induction and 20 mg/m2 during re-induction/consolidation for maximum 6 cycles. Patients were followed for at least 6 months past remission (CR/CRp). Results: 116 patients enrolled and 112 in full analysis set. Median age 71 years. Median DOR (censored at alternative therapy) for CR/CRp was 56 weeks (95% CI, 33 weeks - not yet estimable [n/e]) and for CR 65 weeks (95% CI, 41 weeks - n/e). Median DFS (not censored at alternative therapy) for CR/CRp was 34 weeks (95% CI, 24 - 65 weeks). Median OS was 41 weeks (95% CI 28 - 53 weeks), for CR/CRp 59 weeks (95% CI, 50 weeks - n/e ), and for CR was 72 weeks (95% CI, 53 weeks - n/e) after median follow-up of 36 weeks (range, 1 - 85 weeks). Thirty-day mortality was 9.8% for all patients with 4.7% and 13% for age 1 yr), and DFS and OS compare favorably to historical experience, particularly in patients with these adverse prognostic factors. These results suggest that single agent CLO is an effective and tolerable treatment option for older adult patients with untreated AML and 1 or more unfavorable baseline prognostic factor(s).

15 documents available on INCB18424... couldn't find anything on the Sheddase (7824) product.

Per ASCO...EZN-2968, a novel hypoxia-inducible factor-1α (HIF-1α) messenger ribonucleic acid (mRNA) antagonist: Results of a phase I, pharmacokinetic (PK), dose-escalation study of daily administration in patients (pts) with advanced malignancies. Sub-category: Phase I Studies Category: Developmental Therapeutics: Cytotoxic Chemotherapy Meeting: 2009 ASCO Annual Meeting Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 2564) Abstract No: 2564 Attend this session at the ASCO Annual Meeting! Session: Developmental Therapeutics: Cytotoxic Chemotherapy Type: General Poster Session Time: Saturday May 30, 8:00 AM to 12:00 PM Location: Level 2, West Hall C Personalize your Annual Meeting experience with a suggested or customized itinerary! Author(s): A. Patnaik, E. G. Chiorean, A. Tolcher, K. Papadopoulos, M. Beeram, D. Kee, M. Waddell, E. Gilles, A. Buchbinder; START, San Antonio, TX; Indiana University Cancer Center, Indianapolis, IN; Enzon Pharmaceuticals, Inc., Bridgewater, NJ Abstract: Background: HIF-1 is a transcription factor that regulates expression of many key genes, notably those switching cell metabolism to anaerobic glycolysis and inducing neovascularization in response to hypoxia. Increased HIF-1α levels are associated with poor prognosis in several neoplasms. EZN-2968 is a potent locked nucleic acid antisense oligonucleotide suppressing HIF-1α mRNA translation in vitro (IC50 ~1-5 nM). Methods: This study was designed to determine the safety, tolerability, PK, maximum tolerated dose, recommended dose, and preliminary evidence of antitumor activity of EZN-2968. Pts with advanced malignancies were treated with EZN-2968 administered as a daily 2-hr IV infusion x 5 days every 4 weeks using a 3+3 dose-escalating design. Dose escalation was based on toxicities observed during Cycle 1. Results: 19 pts (11 men; median age = 60 y [47-79 y]) were treated with EZN-2968 doses of 0.5 (3 pts), 0.8 (3 pts), 1.2 (3 pts), 1.8 (4 pts), 2.7 (3 pts), and 4.1 (3 pts) mg/kg/day. Tumor types included colorectal cancer (7 pts); renal cancer (4 pts); soft-tissue sarcoma (STS; 2 pts); angiosarcoma (1 pt); melanoma (1 pt); and breast, ovarian, pancreatic, and prostate cancers (1 pt each). No dose-limiting toxicities were observed. The most common adverse events (Aes) were vomiting (32%); fatigue (26%); and anemia, diarrhea, nausea, and tumor pain (each 21%). Most Aes were Grade 1 or 2. Plasma PK for Day 1 is tabulated below. Stable disease was observed for 1 pt with angiosarcoma (28 wks) and 1 pt with renal cancer (12 wks). Conclusions: EZN-2968 was well tolerated in previously treated pts with advanced malignancies. PK data do not show accumulation of EZN-2968. Dose escalation is ongoing; final results will be presented at the meeting. Durable stable disease has been observed.

A quantitative multigene RT-PCR assay for prediction of recurrence in stage II colon cancer: Selection of the genes in four large studies and results of the independent, prospectively designed QUASAR validation study. Sub-category: Colorectal Cancer (including liver metastases) Category: Gastrointestinal (Colorectal) Cancer Meeting: 2009 ASCO Annual Meeting Citation: J Clin Oncol 27:15s, 2009 (suppl; abstr 4000) Abstract No: 4000 Attend this session at the ASCO Annual Meeting! Session: Gastrointestinal (Colorectal) Cancer Type: Oral Presentation Time: Saturday May 30, 3:00 PM to 5:45 PM Location: Level 2, West Hall D2 Personalize your Annual Meeting experience with a suggested or customized itinerary! Author(s): D. Kerr, R. Gray, P. Quirke, D. Watson, G. Yothers, I. C. Lavery, M. Lee, M. J. O'Connell, S. Shak, N. Wolmark, Quasar Colon Teams; University of Oxford; University of Birmingham Clinical Trials; Leeds Institute of Molecular Medicine; Genomic Health, Inc., Redwood City, CA; NSABP, Pittsburgh, PA; Cleveland Clinic Foundation, Cleveland, OH Abstract: Background: New clinical tools are needed to improve risk assessment and treatment decisions in stage II colon cancer. Four development studies [Surgery (Sx) alone: NSABP C-01/C-02 (n=270) and CCF study (n=765); Sx+5FU/LV: NSABP C-04 (n=308) and C-06 (n=508)] were performed to select the genes for prediction of recurrence and 5FU/LV benefit. To determine clinical utility of the prespecified assay, we performed a large, independent, prospectively designed, clinical validation study in stage II colon cancer pts from the QUASAR trial. Methods: Gene expression was quantitated by RT-PCR from 30 µm manually microdissected fixed paraffin-embedded primary colon cancer tissue. Recurrence-free interval (RFI), disease-free survival (DFS), and overall survival (OS) were analyzed using Cox regression. Results: Combined analysis of the four development studies (total n=1,851; 761 candidate genes) identified 48 genes significantly associated with recurrence risk and 66 genes predictive of 5FU/LV benefit. Multivariate analysis, in the context of stage, grade, nodes examined, and MSI status, yielded 18 genes (7 prognostic genes, 6 predictive genes, 5 reference genes) and separate prognostic recurrence score (RS) and predictive treatment score (TS) algorithms. In the QUASAR validation study, tumor blocks were collected for 68% of pts; 1,490 pts with blocks had stage II colon cancer and RT-PCR was successful in 1,436 eligible pts (711 Sx, 725 Sx+5FU/LV). Median FU=6.6 yrs. In the primary analysis of RFI in pts following Sx, the RS predicted recurrence risk (HR/25 units=1.58, 95% CI 1.15-2.15; p=0.004). The RS also predicted DFS (p=0.01) and OS (p=0.04). Recurrence risk increased monotonically with increasing RS. In multivariate analyses, RS retained prognostic significance (p=0.008) independent of mismatch repair (MMR), T stage, nodes examined, grade, and lymphovascular invasion. MMR deficiency (HR=0.31, 95% CI 0.15-0.63; p

Also on the earlier side of development, Arqule Inc. (ARQL) may have interim data from a mid-stage trial of ARQ-197 in Microphthalmia Transcription Factor tumors - a group of cancers that tend to effect young adults. Last year, Arqule partnered with Japan's Daiichi Sankyo Co. (4568.TO) on the drug.

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