Palifermin
Mechanism :
Though the precise mechanism is unclear, palifermin has been demonstrated to shield the oral and intestinal epithelia from the side effects of chemotherapy and radiation. In patients in the appropriate therapy groups, palifermin, a recombinant keratinocyte growth factor (KGF), may encourage cell proliferation and lessen the severity of oral mucositis. This effect may be primarily brought on by fibroblast growth factor 2 antagonists.
Indication :
- Prophylaxis for mucositis
- Supportive care in individuals with hematologic cancers who are on myelotoxic preparative regimen followed by an autologous hematopoietic stem cell transplantation that is predicted to cause a high incidence of WHO Grade 3 or higher mucositis.
Contraindications :
Non-hematologic carcinoma
Safety and effectiveness of the drug has been un-established in individuals with non-hematologic cancers. Unknown are the effects of palifermin on the stimulation of non-hematopoietic malignancies that express the KGF receptor. Palifermin has been demonstrated to accelerate the growth of tumour cell lines in a human carcinoma xenograft model and human epithelial tumour cell lines in vitro at doses greater than 10 mcg/ml (> 15-fold higher than usual therapeutic dosages in people).
Infertility
Higher risk of male and female infertility with palifermin therapy, based on data from animal studies. Decreased epididymal sperm counts in male rats and increased implantation loss and reduced fertility index in female rats were seen when the drug was administered IV daily at doses that were 5-fold more than the usually suggested dose.
Dosing :
For mucositis prophylaxis:
Palifermin has been unsuccessful in mitigating incidence of severe mucositis in individuals with hematologic cancers on myelotoxic treatment in the setting of allogeneic hematopoietic stem cell support.
As supportive care in individuals with hematologic cancers who are on myelotoxic preparative regimen followed by an autologous hematopoietic stem cell transplantation that is predicted to cause a high incidence of WHO Grade 3 or higher mucositis:
Due to lack of efficacy, palifermin is not suggested for treatment with
melphalan 200 mg/m2 as a conditioning regimen.
IV dosing:
In adults: For a total of 6 doses, a 60 mcg/kg IV bolus injection is administered OD for 3 straight days days prior to myelotoxic therapy and OD for 3 straight days after. Before beginning myelotoxic therapy, administer the first three doses. The third dose should be given 24 - 48 hours prior to myelotoxic therapy. The final three doses should be given after myelotoxic therapy is finished. The first of these doses should be given on the same day as the hematopoietic stem cell infusion but after the infusion is finished and at least 7 days after the most recent palifermin treatment. Never provide myelotoxic chemotherapy within 24 hours of starting it, during it, or 24 hours following it.
Adverse Effect :
>10%: Rash, pyrexia, itching, redness, swelling, high serum lipase, high serum amylase, discoloration of mouth, tongue, loss of protein in urine, altered taste, pain, dysesthesia
1-10%: High blood pressure, formation of antibodies, joint pain
<1%: Cough, vaginal redness, swelling, cataract, perianal pain, rhinitis
Interaction :
Fexinidazole, bleomycin, cyclophosphamide and busulfan are some drugs that can interact with this drug
Lactation :
Palifermin's effects on the breastfed newborn or on milk production as well as if it is secreted in human milk are unknown. Women should stop breastfeeding for at least two weeks following the final dose of palifermin treatment due to the possibility of major adverse effects in a nursing infant.
Pregnanacy :
Palifermin may lead to fetal harm if used during gestation, based on animal data. Increased post-implantation loss and reduced fetal body weights occurred in the off-spring of female rabbits following palifermin doses that resulted about 5 times the exposure (AUC) observed in humans at the recommended dose. Additionally, elevated skeletal variations were reported in the off-spring of female rats who received palifermin doses that led to about 35 times the exposure observed in humans at the usually suggested dose.