Complementary Medicine Use Amongst Patients with Metastatic Cancer Enrolled in Phase III Clinical Trials

Abstract

Background: Complementary medicines (CM) are frequently used by patients with cancer. Controversy exists over the effectiveness and risk that CM may add to conventional cancer therapy. The incidence of CM use among patients enrolled in phase III clinical trials is unknown.

Methods: Medication lists from 6 international phase III clinical trials were retrospectively reviewed to identify patients using CM. Patients had metastatic breast, colorectal, or lung cancers. Quality of life, adverse events, overall survival, and progression-free survival were compared between CM users and non-users. Baseline differences between groups were adjusted with propensity score matching groups.

Results: Seven hundred and six of 3446 patients (20.5%) used at least one CM. CM use was highest among patients with breast cancer (35.6%). CM users had more favorable baseline prognostic factors (ECOG 0-1, non-smoking status, younger age, and fewer metastases). CM use was associated with lower rates of adverse events (50% vs. 62%, P = .002) and quality of life was similar between both groups. After adjustment with propensity score matching, CM use was also associated with longer overall survival in patients with lung cancer (adjusted hazard ratio 0.80, 95%CI, 0.68-0.94, P =.0054). However, several key control variables like EGFR status were not available.

Conclusion: One in 5 patients in phase III clinical trials report using CM. CM was not associated with worse cancer-specific outcomes. However, CM users had more favorable baseline prognostic factors, and likely other confounders that may have contributed to improved outcomes observed in the lung cohort. Physicians should monitor for CM use and potential interactions with clinical trial drugs.

Keywords: cancer; clinical trial; complementary medicine.

Figure 1.

a-d: Kaplan-Meier curves depicting overall survival between complementary medicine (CM) users (n = 706) and non–CM users (n = 2740). Risk of death was lower in CM users (aHR 0.873, 95% CI, 0.735-0.930, P < .001) (a) and among CM users with lung cancer (aHR 0.795, 95% CI, 0.676-0.935, P = .005) (b). No significant differences in OS are noted between CM users and non-users with colorectal cancer (c) or breast cancer (d).

Figure 2.

a-d: Kaplan-Meier curves depicting progression-free survival between complementary medicine (CM) users (n = 706) and non–CM users (n = 2740). Risk of progression was lower in CM users (aHR 0.900, 95% CI, 0.829-0.987, P = .024) (a) and among CM users with lung cancer (aHR 0.834, 95% CI, 0.719-0.968, P = .016) (b). No significant differences in progression-free survival are noted between CM users and non-users with colorectal cancer (c) or breast cancer (d).