Chemotherapy-induced peripheral neuropathy (CIPN) is a common and often long-lasting side effect of cancer treatment. Patients may experience numbness, tingling, pain, burning sensations, weakness, or difficulty with walking and daily activities. Paclitaxel-related CIPN is especially common, and current treatment options are limited. For patients whose symptoms do not improve with standard therapies such as duloxetine, pregabalin, or gabapentin, there is an important unmet clinical need. Papaverine is a vasodilator and smooth muscle relaxant that may improve blood flow in the small vessels supplying nerves. Based on the hypothesis that impaired microcirculation and ischemia may contribute to CIPN, papaverine may help relieve symptoms and support nerve recovery. Preliminary clinical observations by the investigators suggested that papaverine injection may rapidly improve numbness and weakness in some patients with refractory paclitaxel-induced CIPN.This is a prospective, single-center, single-arm, open-label phase II study designed to evaluate the preliminary efficacy and safety of papaverine injection in patients with refractory paclitaxel-induced peripheral neuropathy. Eligible participants are adults aged 18 to 75 years with histologically or cytologically confirmed malignancy, prior treatment with a paclitaxel-containing regimen, persistent clinically significant neuropathy of grade 2 or higher, and failure of at least one standard treatment for CIPN. Participants will receive papaverine hydrochloride 120 mg diluted in 100 mL normal saline by intravenous infusion once daily, given as 1 treatment day followed by 6 rest days, with 7 days defined as one cycle. Up to 3 cycles of treatment may be given if patients benefit and tolerate therapy well.The main goal of the study is to assess improvement in patient-reported sensory neuropathy symptoms using the EORTC QLQ-CIPN20 sensory subscale. Secondary objectives include changes in overall neuropathy symptoms, physician-assessed neuropathy grade, quality of life, and safety. Exploratory assessments include nerve conduction findings and inflammatory biomarkers. The study aims to enroll approximately 43 patients and will provide early evidence on whether papaverine may be a useful treatment option for patients with refractory paclitaxel-induced CIPN.

Inclusion Criteria:

• Age 18 to 75 years.
• Histologically or cytologically confirmed malignancy.
• Prior treatment with a taxane-containing chemotherapy regimen, including but not limited to paclitaxel, docetaxel, or nab-paclitaxel, with completion of chemotherapy at least 4 weeks before enrollment.
• Persistent, clinically significant peripheral neuropathy mainly attributed to taxane-based chemotherapy, with NCI-CTCAE v5.0 sensory neuropathy grade ≥ 2.
• Failure of at least one standard treatment for chemotherapy-induced peripheral neuropathy, such as duloxetine ≥ 60 mg/day, pregabalin ≥ 150 mg/day, or gabapentin ≥ 900 mg/day, for at least 4 weeks, defined as lack of symptom improvement or intolerance to treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate organ function, including hematologic, hepatic, and renal function within acceptable ranges.
• Willingness to participate and ability to provide written informed consent.

Exclusion Criteria:

• Peripheral neuropathy due to causes other than chemotherapy, such as uncontrolled diabetes mellitus (HbA1c > 7.0%), severe renal insufficiency, vitamin B12 deficiency, thyroid dysfunction, or history of alcohol abuse.
• Known hypersensitivity to papaverine or any of its components.
• Contraindications to papaverine, such as complete atrioventricular block.
• Current use of other investigational drugs that may affect neurological function.
• Pregnant or breastfeeding women.
• Severe hepatic or renal dysfunction, defined as ALT or AST > 3 × upper limit of normal or serum creatinine > 2 × upper limit of normal.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in the study.