Hoff, P.M., Saragiotto, D.F., Barrios, C.H., del Giglio, A., Coutinho, A.K., Andrade, A.C., . . . van Eyll, B. (2014). Randomized phase III trial exploring the use of long-acting release octreotide in the prevention of chemotherapy-induced diarrhea in patients with colorectal cancer: The LARCID trial. Journal of Clinical Oncology, 32(10), 1006–1011. 

To evaluate the efficacy and safety of long-acting release (LAR) octreotide for the prevention of chemotherapy-induced diarrhea (CID)

This prospective, randomized clinical trial compared the administration of octreotide LAR 30 mg IM every four weeks beginning with first-cycle to the administration of a physician’s choice of medication in a group of patients with colorectal cancer starting adjuvant or first-line treatment. Patients received combination chemotherapy with fluorouracil, capecitabine, and/or irinotecan. Treatment with octreotide LAR was continued for six months or until chemotherapy discontinued or until the patient developed unacceptable toxicity related to the study drug (whichever occurred first). The choice for the treatment for diarrhea for both arms was at the physicians' discretion, but the control group could not receive octreotide LAR. Patients were stratified according to the use of irinotecan.

• N = 139  
• AGE RANGE = 22–78 years
• MALES: Treatment group 45.6%; control group 42.3%, FEMALES: Treatment group 54.4%; control group 57.7%
• KEY DISEASE CHARACTERISTICS: Patients with colorectal cancer starting adjuvant or first-line treatment with combination chemotherapy containing fluorouracil, capecitabine, and/or irinotecan.
• OTHER KEY SAMPLE CHARACTERISTICS: Sites of metastatic disease, colostomy, and type of surgery

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Brazil at multiple institutions

• PHASE OF CARE: Active antitumor treatment

Randomized, multi-centered, open-labeled, phase III trial

• To evaluate the incidence and severity of diarrhea, a patient diary was given to patients at each visit, and the completed tool was collected at the next visit. The diary was used to record patient events. 
• All adverse events (related to laboratory or dose reductions) were collected through medical records.
• A Functional Assessment of Chronic Illness Therapy For Patients With Diarrhea (FACIT-D) scale was collected at each visit. 

139 patients were randomly assigned. Most received a fluorouracil (treatment  98.5%, control  98.6%) or oxaliplatin (treatment 76.5%, control 63.4%) containing regimen. The rate of diarrhea was 76.1% in the treatment group (n = 68) and 78.9% in the control group (n = 71). Treatment with octreotide LAR did not prevent or reduce the severity of chemotherapy-induced diarrhea.

There was no benefit in using octreotide LAR prophylactic in patients with colorectal cancer starting adjuvant or first-line treatment with combination chemotherapy containing fluorouracil, capecitabine, and/or irinotecan.

• Risk of bias (no blinding)
• There was a small number of patients who received chemotherapy with other regimens containing irinotecan. There was also the smaller proportion of patients presenting with grade 3 or 4 diarrhea. 

There was no benefit in using octreotide LAR prophylactic in patients with colorectal cancer starting adjuvant or first-line treatment with combination chemotherapy containing fluorouracil, capecitabine, and/or irinotecan. This has also been evaluated in other studies that have looked at octreotide LAR using escalation doses of 30 or 40 mg, and the results were similar. Per the authors of this study, the short-acting octreotide remains the formulation of choice in the treatment of CID.