2104P - Prevention of taxane chemotherapy induced nail changes and peripheral neuropathy by application of extremity cooling: A prospective single center study with intrapatient comparison

Background

Common side effects of taxanes are nail toxicity (tox) and CIPN. Different methods of cryotherapy to prevent these side effects have been tested. We investigated machine-controlled cooling of hand and feet to reduce nail tox and CIPN.

Methods

Patients (pts) receiving Docetaxel (Doce) (planned dose 300mg/m²) or Paclitaxel (Pacli) (planned dose 720mg/m) in the adjuvant or palliative setting were included. The dominant hand and foot were cooled to approximately 10°C using the Hilotherapy-machine. The contralateral hand and foot were used as intrapatient comparison. Primary endpoint was the occurrence of any nail tox (Doce cohort) or CIPN (Pacli cohort) at any time during and up to 56 days after the end of treatment. We assumed an absolute improvement of 40% in nail tox and 20% in CIPN. With 90% power using a two-sided McNemar test with a significance level of 5%, a total of 30 pts were needed in each group. The intended to treat population (ITT) and the per protocol population (PPP) were analysed. Toxicity was assessed using the CTCAE v5.0 grading system and the PNQ questionnaire.

Results

69 pts, 21 (9 in the PPP) treated with Doce and 48 (34 in the PPP) treated with Pacli, were included from 08/2020 - 08/2022. In the Doce cohort, nail tox was not significantly improved by cooling in the ITT (81.0%, vs 85.7%; odds ratio (OR) 0.71, 95% CI: 0.14 – 3.64, p = 0.564) and PPP (100% vs 100%; OR: 1.00, 95% CI: 0.00 – NA, p = NA) but significant benefit across visits over time was found for the ITT (OR: 0.42, 95% CI: 0.18 – 0.98, p=0.045) but not the PPP (OR: 0.75, 95% CI: 0.30 – 1.86, p=0.529). In the Pacli cohort, CIPN was numerically better in the ITT (60.9% vs. 71.7%, OR: 0.61, 95% CI: 0.26 – 1.47, p=0.059) and significantly better in the PPP (67.6% vs. 82.4%, OR: 0.45, 95% CI: 0.14 – 1.40, p-value = 0.025). Differences across visits were significantly in favour of cooling (ITT: OR: 0.28, 95% CI: 0.13 - 0.57, p=0.001; PPP: OR: 0.25, 95% CI: 0.12 - 0.55, p=0.001). Cooling was well tolerated, only 6 pts (9%) discontinued due to side effects.

Conclusions

Cooling of hand and feet has a clinically meaningful impact on occurrence of CIPN and nail toxicity. Effects are more significant over time and are taxane dose dependent.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Kantonsspital Graubünden, Chur, Switzerland.

Funding

Has not received any funding.

Disclosure

R. Cathomas: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Bayer, MSD, Roche, Sanofi, Astellas, Ipsen, Merck, Pfizer, Debiopharm; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Janssen, Merck; Financial Interests, Institutional, Invited Speaker: Astellas; Non-Financial Interests, Member of Board of Directors: SAKK Swiss Working Group for Clinical Cancer Research. All other authors have declared no conflicts of interest.