Phase II Trial of Adjuvant Oral Thalidomide Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Disease from Colorectal/Appendiceal Cancer

Abstract

Purpose This phase II single-institution trial of adjuvant thalidomide after cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with appendiceal and colorectal malignancies sought to detect an improvement in progression-free survival (PFS) from 7 to 12 months. Methods Eligible patients received CS, HIPEC, and baseline imaging, followed by pretreatment thalidomide counseling. All participants were then started on a 28-day regimen of thalidomide, 100 mg by mouth at bedtime, followed by 200 mg for 4 weeks, followed by 300 mg as the final maintenance dose, as tolerated. Results Twenty-seven eligible patients (median age 52 years; 52%appendiceal/48%colorectal) were enrolled on this trial and included in the analysis, and 26 were evaluable for response. Eighteen patients demonstrated stable disease on adjuvant thalidomide, while eight showed evidence of progression. Approximately 30 % of the patients withdrew due to toxicity. Grade 3/4 toxicities included neurological disorders (16 %), nausea (12 %), vomiting (8 %), and thromboembolism (8 %). Median overall survival (OS) and PFS were 43.0 and 9.3months, respectively, and median follow-up was 40.4 months. Multivariate modeling showed significant improvements in PFS and OS for appendiceal patients and those with R0 or R1 resections. On an intent-to-treat analysis, the PFS of the study group was 9 months. Conclusions Based on these findings, thalidomide cannot be recommended as adjuvant therapy after CS and HIPEC for gastrointestinal malignancies. Further research is needed to identify active agents in this population.

The role of chemotherapy in the treatment of advanced appendiceal cancers: summary of the literature and future directions

“…A total of 65 articles were found to be relevant for this review: 33 evaluating the role of HIPEC (Table 4) and 42 evaluating systemic chemotherapy (Table 5), each including 10 articles that reported on both. 6,8–10,12,14–16,21,26,35–91 Table 6 is a summary of the characteristics of the literature included in this r...…”

“…The other prospective trial of perioperative chemotherapy assessed the role of postoperative thalidomide following CRS-HIPEC in 27 participants of whom 14 had appendiceal cancer. 68 The median PFS was 9.3 months and failed to meet the prespecified threshold. Given the limited role of anti-angiogenic agents in the unresectable setting, it is unlikely that this treatment will be pursued further in the perioperative setting.…”