{'fraction_non_alphanumeric': 0.03010204081632653, 'fraction_numerical': 0.025510204081632654, 'mean_word_length': 4.924471299093655, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Early outcome of a phase I study of interrupted pulse dosed axitinib combined with FOLFOX or FOLFIRI in refractory metastatic colorectal cancer.

473 Background: In mCRC, bevacizumab studies have shown improved survival in 5-FU based chemotherapy. Therapeutic inhibition of angiogenesis pathways may improve response of chemotherapy refractory malignancies. We evaluated the combination of axitinib, a VEGF receptor inhibitor, used intermittently with 5-FU based chemotherapy for refractory mCRC. We hypothesized that intermittent pulse dosed axitinib may improve response by delivering chemotherapy during tumor reperfusion after release from angiogenesis inhibition. We present preliminary data of the Phase I portion evaluating the safety and efficacy of interrupted pulse dosed axitinib + FOLFIRI.


METHODS
Initially, Pfizer A4061020 was a phase IB study of axitinib + bevacizumab + FOLFOX vs. FOLFIRI to evaluate potential overlapping toxicities. In cohorts 8 and 9, A4061020 was expanded to determine the MTD of 7 days of intermittent pulse dosed axitinib at 14mg vs. 20mg + FOLFIRI or FOLFOX. Enrollment was open to mCRC with progression on both oxaliplatin and irinotecan-based regimens. The primary outcome was MTD; while secondary outcomes included: PFS, TTP, and OS.


RESULTS
Preliminary data of 10 mCRC subjects show intermittent pulse dosed axitinib at 14mg and 20mg in combination treatment is safe and tolerable (few grade 3 and one grade 4 AE). We observed PFS up to 16.8 mos (avg 8.7 mos, 6 subjects) and TTP up to 17.1 mos (avg 11.8 mos, 4 subjects) vs. average 6 mos on the last line of chemotherapy. To date, the OS endpoint has not been achieved ( Table ).


CONCLUSIONS
In 10 heavily pre-treated mCRC subjects, intermittent pulse dosed axitinib demonstrates safety, tolerability, and improved PFS and TTP. Intermittent pulse-dosed VEGF receptor inhibition may enhance tumor response that warrants further exploration. [Table: see text].