Randomized controlled trial of cryotherapy to prevent paclitaxel-induced peripheral neuropathy (RU221511I); an ACCRU trial

Abstract

Purpose: This pilot trial aimed to assess if cooling hands and feet with crushed ice during receipt of paclitaxel helps prevent peripheral neuropathy.

Methods: This prospective, randomized trial compared cryotherapy to standard care in patients initiating paclitaxel weekly x 12. For those on cryotherapy, hands and feet were cooled starting 15 min prior to and ending 15 min after each paclitaxel dose. EORTC QLQ-CIPN20 was completed at baseline, weekly x12, then monthly x6. Area under the curve (AUC) was calculated for subscale scores, adjusting for baseline, and compared between arms (Wilcoxon rank-sum test). Cross-study comparisons used data from 2 prior similarly-conducted neuropathy trials.

Results: Forty-six patients were accrued. Three withdrew and one was ineligible. Of the remaining 42 (21 cryotherapy, 21 control), 39 (19 cryotherapy, 20 control) were analyzable for AUC. Cryotherapy was well tolerated, but the AUC of the CIPN20 sensory scores over 12 weeks of paclitaxel was not found to differ between the study arms (mean difference 3.45, 95% CI -3.13 to 10.02, p = 0.26). However, the control arm of the current trial experienced less neuropathy than did the placebo arms of two previous similar trials. When our cryotherapy arm was compared to the combined control arms from all three trials, the cryotherapy arm had less neuropathy (Wilcoxon Rank-Sum p = 0.01).

Conclusion: While there was no difference in CIPN20 scores identified between the 2 study arms in the current phase II trial, further investigation is needed given that the control arm experienced less neuropathy than was expected.

Keywords: Chemotherapy-induced neuropathy; Cryotherapy; Paclitaxel acute pain syndrome; Paclitaxel-associated neuropathy.

Figure 1:

CONSORT diagram

Figure 2:

CIPN during 12 weeks of treatment and 6 months of follow-up represented as the mean change from baseline in EORTC QLQ-CIPN20 sensory scores. Higher scores represent fewer symptoms.

Fig. 3

Mean change from baseline in EORTC QLQ-CIPN20 selected individual item scores during treatment and over 6-month follow-up for tingling fingers/hands (a), tingling toes/feet (b), numbness fingers/hands (c), numbness of toes/feet (d), shooting burning pain of fingers/hands (e), and shooting burning pain of toes/feet (f). Higher scores represent fewer symptoms.

Fig. 3

Mean change from baseline in EORTC QLQ-CIPN20 selected individual item scores during treatment and over 6-month follow-up for tingling fingers/hands (a), tingling toes/feet (b), numbness fingers/hands (c), numbness of toes/feet (d), shooting burning pain of fingers/hands (e), and shooting burning pain of toes/feet (f). Higher scores represent fewer symptoms.

Figure 4:

Mean worst pain daily scores over 6 days following paclitaxel doses for each cycle. Higher scores represent more pain.

Figure 5:

CIPN during 12 weeks of treatment represented as the mean change in EORTC QLQ-CIPN20 sensory scores for patients participating in the current trial and in two prior trials that had evaluated minocycline and pregabalin, using virtually identical protocol methodologies. Higher scores represent fewer symptoms. Figure 5A illustrates data with the individual control arms for the 3 trials shown separately, while 5B combines the control arms into one line.