Protective Effect of Pentoxifylline Against Chemotherapy Induced Toxicities in Patients With Colorectal Cancer

• Status: Enrolling by invitation
• Trial end date: 2024-10-11
• Target enrollment: 0
• Participant gender: All

Summary

This study aims to:

• Evaluate the possible protective effect of pentoxifylline against oxaliplatin induced peripheral neuropathy and chemotherapy induced mucositis in patients with stage II and stage III colorectal cancer.

This study will be a randomized placebo controlled parallel study.48 patients with colorectal cancer will be randomized to 2 groups:

Group I (control group; n=24) which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily. Group II (Pentoxiphylline group; n=24) which will receive FOLFOX-6 regimen in addition to pentoxifylline 400 mg twice daily.

Blood sample collection and biochemical assessment:

• Malondialdehyde (MDA) as oxidative stress marker (colorimetry).

• Tumor necrosis factor alfa (TNF-α) as pro inflammatory marker (ELISA).

• Neurotensin (NT) as a potential marker for neuropathic pain (ELISA).

• Citrulline as a biomarker for mucositis (ELISA).

Clinical assessment of oxaliplatin induced neuropathy will be done through:

The assessment of the severity of neuropathic pain through "Brief Pain Inventory-Short Form" at baseline and by the end of every two chemotherapy cycles.

The implication of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017) for grading of neuropathy every 2 cycles. The use of Neurotoxicity- 12 item questionnaire score (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group at baseline and by the end of every two chemotherapy cycles).

Mucositis will be assessed at baseline and by the end of every two chemotherapy cycles through the use of common terminology criteria for adverse events "CTCAE, version 5.00, 2017

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tanta University
• Treatments: Fluorouracil; Leucovorin; Oxaliplatin; Pentoxifylline

Criteria

Inclusion Criteria:

• - Patients with histologically confirmed diagnosis of stage II and stage III colorectal cancer.

• Patients who will be scheduled to receive FOLFOX-6 regimen.

• Patients with no contraindication to chemotherapy.

• Males and females aged ≥ 18 years old.

• Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5

× 109/L, platelet count ≥ 100 × 109/L and hemoglobin level ≥ 10 g/dl).

• Patients with adequate renal function (serum creatinine < 1.5 mg/dL and Creatinine clearance (ClCr) ˃ 45 mL/min).

• Patients with adequate liver function (serum bilirubin < 1.5 mg/dl).

• Patients with performance status < 2 according to Eastern Cooperative Oncology Group (ECOG) score.

Exclusion Criteria:

• - Children < 18 years old.

• Prior exposure to neurotoxic chemotherapy (oxaliplatin, cisplatin, vincristine, paclitaxel, docetaxel or Isoniazid) for at least 6 months prior the study treatment.

• Evidence of pre-existing peripheral neuropathy resulting from another reason (diabetes, brain tumor or brain trauma).

• Patients with diabetes and other conditions that predispose to neuropathy as hypothyroidism, autoimmune diseases or hepatitis C.

• History of known allergy to oxaliplatin or other platinum agents.

• Patients with other inflammatory diseases (rheumatoid arthritis and ulcerative colitis) or stressful conditions (obesity class 2 and 3, smoking).

• Concomitant use of multivitamins (vitamins E, C and A), tricyclic antidepressants or other neuro-protective medications (gabapentin, lamotrigine, carbamazepine and phenytoin, etc...).

• Concurrent active cancer originating from a primary site other than colon or rectum.

• Patients on blood thinning agents

• Pregnant and breastfeeding women