Indiana University, Indianapolis, IN
Aabha Oza , Patrick Grierson , Sean Glasgow , Katrina Pedersen , Stephen Barman , Thomas Westbrook , Matthew G Mutch , Andrea Wang-Gillam , Rama Suresh , Ashley Morton , Samantha Marquez , James W Fleshman , Benjamin R. Tan Jr.
Background: Peritoneal carcinomatosis (PC) is the intraperitoneal spread of cancer. Optimal treatment for PC is controversial. Systemic chemotherapy offers limited benefit (Franko, 2011). Intraperitoneal (IP) chemotherapy following cytoreductive surgery (CRS) improves outcomes (Verwaal, 2008). Oxaliplatin (Ox), capecitabine, and bevacizumab are standard agents for the treatment of metastatic colorectal cancer (CRC). Evidence suggests benefit of IP Ox at high doses. However, the optimal dose of IP Ox combined with standard systemic therapy is unclear. Methods: We conducted an IRB-approved phase I dose-escalation study of IP Ox D1 at 25mg/m2-100mg/m2, with systemic bevacizumab D1 at 5mg/kg, and capecitabine 850mg/m2 BID for 7 days (cycle = 14 days), in patients with PC from appendiceal or CRC after CRS. The primary aim was to determine the recommended phase II dose (RP2D)/maximum tolerated dose (MTD) for this regimen. Dose limiting toxicities (DLTs) were assessed during cycle 1. DLTs included grade 3 or 4 non-hematological toxicities, or grade 4 hematological toxicities. Results: 18 patients (12 females, median age 56) were enrolled on the study. No DLTs were observed during cycle 1 in the first 4 cohorts. One DLT (abdominal pain) was observed in cohort 5. Another patient in cohort 5 experienced grade 3 abdominal pain soon after cycle 2, thus limiting repeated treatment for this cohort. Other toxicities included fatigue (72%), nausea (61%), peripheral neuropathy (50%), constipation (50%), mucositis (39%) and dizziness (39%). See table below for average # of cycles per cohort and responses. Conclusions: IP Ox combined with capecitabine and bevacizumab is feasible. Our recommended dose for IP Ox is 85 mg/m2 with systemic therapy (cohort 4). An expansion cohort is underway for this dose level. Based on these data, further investigation of IP Ox with systemic chemotherapy for PC is warranted. Clinical trial information: NCT01061515
IP Ox Dose Level | |||||
---|---|---|---|---|---|
1 (25mg/m2) | 2 (50mg/m2) | 3 (65mg/m2) | 4 (85mg/m2) | 5 (100mg/m2) | |
N | 5 | 4 | 3 | 3 | 3 |
Average # of cycles (range) | 10.2 (4-19) | 4 (0-9) | 9.3 (7-12) | 9.6 (4-17) | 6.7 (1-8) |
# DLT | 1 | 2 | 0 | 0 | 1 |
CR/PR | 1 | 0 | 1 | 1 | 0 |
SD | 3 | 2 | 1 | 2 | 0 |
PD | 1 | 1 | 1 | 0 | 1 |
N/A | 0 | 1 | 0 | 0 | 2 |
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