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Study of the preventive effect of laftidine for chemotherapy-induced peripheral neuropathy in patients receiving paclitaxel

SHIVILE study

16

In total, 18 patients were screened, and 16 were randomly assigned to one of the groups between January 2021 and January 2023. Nine were assigned to the lafutidine group and 7 to the control group. The median age was 68 years in the lafutidine group and 73 years in the control group. Fifteen patients (93.8%) were male and ECOG PS of all patients was 1 or 2. Only 1 patient in the control group harbored the EGFR mutation. All patients received the combination of carboplatin and paclitaxel, not in combination with bevacizumab or immune checkpoint inhibitors. Overall, 7 patients (43.8%) had stage IV disease, and 9 (56.3%) stage III or less. Total dose (median) of paclitaxel was 1,143 mg in both groups.

The number of patients included in the analysis was less than the target number. One reason for the difficulty in enrolling patients may have been the increased use of nab-PTX as an alternative to PTX.

Adverse events were not seen including unexpected AE.

<Primary outcome> The incidence of Grade 2 or higher neuralgia in CTCAE version 5.0; 22% in the lafutidine group and 14.3% in the control group, was not statistically significantly different. The incidence of Grade 2 or higher peripheral sensory neuropathy in CTCAE version 5.0; 100% in the lafutidine group and 71.4% in the control group, was not statistically significantly different.. <Secondary outcome> The incidence of Grade 3 or higher peripheral neuropathy in CTCAE version 5.0 was not found in either group. Distribution of peripheral neuropathy scores on the Japanese version of the Patient Neurotoxicity Questionnaire (PNQ); Median PNQ scores were not statistically significantly different between the two groups at all assessments. Distribution of peripheral neuropathy scores on the Japanese version of the Functional Assessment of Cancer Therapy-neurotoxicity (FACT/GOG-Ntx); Median FACT/GOG-Ntx scores were not statistically significantly different between the two groups at all assessments. However, the median FACT/GOG-Ntx score after 4 cycles of treatment tended to be lower in the lafutidine group than in the control group. Median time to appearance of grade 2 or higher peripheral neuropathy; There was no statistically significant difference in the onset time of peripheral neuropathy between the two groups. Percentage of paclitaxel dose reduction or discontinuation due to adverse events; There was no statistically significant difference in the number of patients in the lafutidine group (3 patients, 33.3%) and the control group (3 patients, 42.9%) who reduced the dose of paclitaxel due to adverse events. No patients discontinued paclitaxel due to adverse events between the two groups. Progression Free Survival (PFS); Median PFS was 147 days in the lafutidine group and 217.5 days in the control group, with no statistically significant difference between the two groups. Response rate (RR); Median response rate was 78% in the lafutidine group and 85% in the control group, with no statistically significant difference. Safety (incidence of adverse events); No adverse events due to lafutidine administration were found in this study.

This study was a prospective randomized trial to evaluate the preventive effect of lafutidine on Chemotherapy induced peripheral neuropathy (CIPN). Although the preventive effect of lafutidine on CIPN could not be statistically proven, the FACT/GOG-Ntx score showed a trend toward decreased neurotoxicity with lafutidine treatment.

Sept. 18, 2023

Sept. 18, 2023

https://dx.doi.org/10.21037/apm-23-90

No

None.

https://jrct.mhlw.go.jp/latest-detail/jRCTs021200031

Nagashima Hiromi

Iwate Medical University Hospital

2-1-1 Idaidori Yahaba Shiwa Iwate

hironaga@iwate-med.ac.jp

Cho Katsuya

Iwate Medical University Hospital

2-1-1 Idaidori Yahaba Shiwa Iwate

+81-19-613-7111

chokatu@iwate-med.ac.jp

Complete

Dec. 15, 2020

Interventional

randomized controlled trial

open(masking not used)

no treatment control/standard of care control

single assignment

prevention purpose

1.The age at the time of obtaining consent is 18 years or older
2.Patients with cytopathological or clinical diagnosis of non-small cell lung cancer
3.Cases where surgical treatment, definitive radiation therapy, and chemoradiation therapy are not indicated (excluding palliative irradiation)
4.Patients scheduled to be treated by the treatment including paclitaxel
5.Patients scheduled to treated by carboplatin+paclitaxel therapy (batch) or carboplatin+paclitaxel (batch) +pembrolizumab therapy
(or patients with Grade 2 or higher (CTCAE ver5.0.) CIPN by split paclitaxel)
6.Patients who are not recieving anti-ulcer drugs or are receiving anti-ulcer drugs but are considered to be able to change to lafutidine
7.Patients who can ingest orally
8.Patients who can recieve informed consent

1.Patients who receive paclitaxel as chemoradiotherapy
2.Patients who are pregnant or breastfeeding
3.Patients with a history of drug hypersensitivity or allergy to lafutidine
4.Patients with a history of drug hypersensitivity or allergy to paclitaxel
5.Patients with contraindications reg arding paclitaxel administration, such as those with a history of hypersensitivity to polyoxyethylene castor oil-containing preparations (eg, cyclosporine injection) or severe myelosuppression
6.Patients with a history of severe drug hypersensitivity to other drug s
7.Patients who have already taken anti-ulcer drugs and cannot chang e to lafutidine
8.Patients who cannot judg e subjective symptoms related to peripheral neuropathy due to sympto
ms by brain metastasis or neuropathy
9.Patients originaly had Grade2(CTCAE ver5.0.) or higher peripheral neuropathy
10.Patients judg ed to be inappropriate by doctor to safely carry out this reserch

Both

Non Small Cell Lung Carcinoma

20 patients in the intervention group/20 patients in the control group.In the intervention group, raftidine 10mg tablets will be taken twice a day in the after breakfast and after dinner.In the control group, nothing will be taken.

Common Terminology Criteria for Adverse Events(CTCAE) version 5.0.: Grade 2 or higher peripheral neuropathy

Common Terminology Criteria for Adverse Events(CTCAE)version 5.0:Grade 3 or higher peripheral neuropathy
Peripheral neuropathy score distribution in the Patient Neurotoxicity Questionnaire (PNQ)
Peripheral neuropathy score distribution in the Functional Assessment of Cancer Therapy-neurotoxicity(FACT/GOG-Ntx)
Time from the first cycle therapy of paclitaxel to the appearance of peripheral neuropathy
Rate of dose reduction / discontinuation of paclitaxel due to adverse events
Progression Free Survival,PFS
Response Rate,RR
Safety(occurrence of adverse events)

+81-19-651-5111

Nov. 09, 2020

none