Phase II trial of adjuvant oral thalidomide following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface disease from colorectal/appendiceal cancer.
OBJECTIVE
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 9.3 months, 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.
Surgical Oncology Service, Wake Forest Baptist Health, Medical Center Boulevard, Winston-Salem, NC, 27157, USA, pshen@wakehealth.edu.
Perry
P
Shen
Christopher R
CR
Thomas
Joyce
J
Fenstermaker
Mebea
M
Aklilu
Thomas P
TP
McCoy
Edward A
EA
Levine
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery / Q000628:therapy; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001063:Appendiceal Neoplasms / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000601:surgery; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D007263:Infusions, Parenteral; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009422:Nervous System Diseases / Q000139:chemically induced; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery / Q000628:therapy; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013923:Thromboembolism / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D013792:Thalidomide