Breast cancer is the most frequently diagnosed cancer in the world. In France, 58,000 new cases were detected in 2018. Breast cancer is therefore the most common cancer in women. The 5-year survival rate for all stages combined is 88%. These excellent survival figures have been achieved thanks to improvements in treatment, including the advent of chemotherapy. The majority of patients will be cured of their cancer, so post-cancer quality of life is a major issue, hence the importance of trying to reduce long-term sequelae.
Taxanes are one of the main cytotoxic anticancer agents used in the treatment of breast cancer. However, taxanes have a direct effect on the central and peripheral nervous systems and can induce chemotherapy-induced peripheral neuropathy (CIPN). The mechanisms of NPIC by taxanes are not fully understood. CINP is manifested by symptoms of paresthesia, numbness, burning, pain, altered temperature perception, myalgia, myopathy, fine motor difficulties, gait and balance disturbances, muscle weakness in the lower limbs and/or functional decline.
NPIC occurs in 80 to 97% of patients treated with taxanes and is the main limiting toxicity during paclitaxel administration. NPIC often leads to postponement or reduction of dose, or even discontinuation of treatment. In addition, NPIC may last for several months or even years after the end of anti-cancer chemotherapy and represents the main long-term sequelae. This can promote and/or exacerbate symptoms of psychological distress (depressive symptoms and symptoms of anxiety) and lead to a reduction in quality of life (QoL). Prevention of NIPC is therefore a major issue in breast cancer treatment. According to the 2014 guidelines from the American Society of Clinical Oncology, prevention and treatment of IPN are inadequate with current weapons, and there is an urgent need to evaluate and find new methods of prevention. One of the challenges in the management of NIPC will be to reduce the pain induced without diminishing the anti-tumour effect of anti-cancer agents.
In recent years, the effectiveness of cryotherapy using a frozen glove and compression therapy using surgical gloves (SG) in preventing taxane-induced PINC has been reported. During chemotherapy, patients wore a frozen glove on one hand and two surgical gloves of the same size on the other hand continuously. Recent study explained how compression therapy and cryotherapy shared a similar mechanism of reducing drug exposure due to vasoconstriction during paclitaxel infusion. The low temperature associated with cryotherapy would reduce paclitaxel uptake and peripheral nerve damage, or mechanotransduction, and allow a reduction in NIPC.
To date, no study has investigated the efficacy of combining the two means of prevention. The current standard at the Centre Antoine Lacassagne is cryotherapy. The aim of this prospective, self-controlled trial is therefore to compare the efficacy of cryotherapy combined with compression prevention versus cryotherapy alone in preventing paclitaxel-induced peripheral neuropathy in patients undergoing adjuvant treatment for localised breast cancer.
Patient age ≥ 18 years ;
Performance Status (PS): 0 to 2
Women with localised or locally advanced breast cancer of any histology
Indication for treatment with 3 to 4 cycles of paclitaxel (+/- trastuzumab, pertuzumab, carboplatin or endoxan) as adjuvant or neoadjuvant therapy. The choice of the number of cycles will be at the investigator's discretion.
Patient age < 18 years
Patients diagnosed with metastatic or bilateral breast cancer
Patients with metastatic disease of any location
Peripheral neuropathy grade ≥ 2 according to CTCAE version 5.0 of the upper or lower limbs
Single group
cryotherapy alone of the upper or lower limbs
DeviceSelf-controlled trial with only standard cryotherapy. Compression glove and foot sock will only be worn on one hand and one leg on the same side allocated by randomisation
cryotherapy and crompression of the upper or lower limbs
DeviceSelf-controlled trial adding compression to standard cryotherapy. Compression glove and foot sock will only be worn on one hand and one leg on the same side allocated by randomisation
To compare the efficacy in preventing peripheral neuropathy as determined by medical staff between cryotherapy treatment alone and combined cryotherapy and compression treatment of the upper limbs in patients treated with paclitaxel.
The limb with the highest grade of neuropathy will be given a score of 1 and the limb with the lowest grade of neuropathy a score of 0. If no neuropathy is identified in either of the 2 limbs, a score of 0 will be given for each limb. Finally, if a neuropathy of the same grade is identified in each of the 2 limbs, a score of 1 will be assigned for both limbs. Success is defined as a differential of -1 in neuropathy score in favour of double prevention. This method will be applied to the primary and secondary endpoints.
To compare the efficacy of cryotherapy alone and combined cryotherapy and compression treatment of the upper limbs in reducing the occurrence of peripheral neuropathy as determined by medical staff throughout the course of treatment.
Differential between the two upper limbs
To compare the efficacy of cryotherapy alone and combined cryotherapy and compression treatment of the lower limbs in reducing the occurrence of peripheral neuropathy as determined by medical staff throughout the course of treatment.
Differential between the two upper limbs
To compare the efficacy of cryotherapy alone and combined cryotherapy and compression treatment of the lower limbs in reducing the occurrence of peripheral neuropathy as determined by the patient throughout the course of treatment.
Differential between the two lower limbs
Comparing cryotherapy tolerance rates with and without compression
Rate of discontinuation of cryotherapy during treatment
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Centre Antoine Lacassagne
Lead sponsor
Thuasne
Collaborator
