A phase I dose-escalation trial of intraperitoneal oxaliplatin with systemic capecitabine and bevacizumab following cytoreduction in patients with peritoneal carcinomatosis from appendiceal or colorectal cancer.

Authors

null

Aabha Oza

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.

Organizations

Indiana University, Indianapolis, IN, Washington University in St. Louis, St. Louis, MO, Washington University School of Medicine in St. Louis, St. Louis, MO, Mayo School of Graduate Medical Education, Rochester, MN, Universtiy of Texas Southwestern Medical Center, Dallas, TX

Research Funding

Other

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)
N54333
Average # of cycles (range)10.2
(4-19)
4
(0-9)
9.3
(7-12)
9.6
(4-17)
6.7
(1-8)
# DLT12001
CR/PR10110
SD32120
PD11101
N/A01002

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Abstract Details

Meeting

2018 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Cancers of the Colon, Rectum, and Anus

Track

Cancers of the Colon, Rectum, and Anus

Sub Track

Multidisciplinary Treatment

Clinical Trial Registration Number

NCT01061515

Citation

J Clin Oncol 36, 2018 (suppl 4S; abstr 746)

DOI

10.1200/JCO.2018.36.4_suppl.746

Abstract #

746

Poster Bd #

J12

Abstract Disclosures