Palifermin for Oral Mucositis after Intensive Therapy for Hematologic Cancers
- Study type
- Clinical trial
- Design
- Randomised, double-blind, placebo-controlled trial
- Sample size
- 212 patients (106 in each group)
- Source
- N Engl J Med · 2004
In plain words
Painful sores and inflammation in the mouth (oral mucositis) are a common side effect of the very intensive treatments given before stem cell transplantation for blood cancers. In this study, a medicine called palifermin was compared with a placebo (dummy treatment). Patients who received palifermin had severe mouth sores less often, for a shorter time, had less pain, and needed strong painkillers and feeding through a vein less often. The medicine's side effects were mostly mild to moderate and short-lived (such as rash, itching and a change in taste).
Key results
Treatment arms and regimens
Conditioning regimen (both groups, per the FDA label): fractionated TBI to a total dose of 12 Gy + high-dose etoposide 60 mg/kg + high-dose cyclophosphamide 100 mg/kg, followed by autologous stem cell infusion.
Palifermin (recombinant human keratinocyte growth factor): 60 µg/kg/day IV for 3 consecutive days immediately before the start of the conditioning regimen and 3 consecutive days after stem cell infusion (6 doses in total). 106 patients.
Administration per the FDA label: IV bolus injection; the third dose 24 to 48 hours before the start of myelotoxic therapy; the first post-treatment dose on the day of stem cell infusion, after the infusion is complete and at least 7 days after the last previous dose. If heparin is used to keep the line open, flush the IV line with normal saline before and after the injection (heparin increases systemic exposure to palifermin).
The same conditioning regimen (TBI 12 Gy + etoposide 60 mg/kg + cyclophosphamide 100 mg/kg) and IV placebo on the same schedule (3 days before conditioning and 3 days after transplantation). 106 patients.
Source of the regimen details: Abstract of the paper and the FDA label for Kepivance (DailyMed, sections "14.1 Clinical Studies — Study 1" and "Dosage and Administration")
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with haematological malignancies (non-Hodgkin lymphoma, Hodgkin disease, acute myeloid leukaemia, acute lymphoblastic leukaemia, chronic myeloid leukaemia, chronic lymphocytic leukaemia or multiple myeloma; per the FDA label) receiving a conditioning regimen of fractionated total body irradiation (TBI) with high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation. Other eligibility criteria in the full text of the paper.
Endpoints
Primary endpoint (per the FDA label): number of days of severe oral mucositis (WHO grade 3 or 4; grade 3 = ulcers and liquid diet only, grade 4 = oral alimentation impossible). Other analyses: incidence, duration and severity of oral mucositis, patient-reported mouth and throat soreness, opioid analgesic use and need for total parenteral nutrition. Daily assessment up to 28 days after transplantation.
Safety and side effects
In the abstract: adverse events were mainly rash, pruritus, erythema, mouth and tongue disorders and altered taste, mild to moderate and transient. Per the FDA label, in pooled data from 409 patients there was no delay in haematopoietic recovery; grade 3 skin rash occurred in 3% of palifermin recipients versus 2% with placebo; reversible increases in serum lipase and amylase (mostly salivary amylase) were common. The label warns about possible stimulation of growth of non-haematological tumours expressing the KGF receptor.
Clinical significance and place in guidelines
This trial was the basis of the FDA approval of palifermin (Kepivance) to decrease the incidence and duration of severe oral mucositis in patients with haematological malignancies receiving myelotoxic therapy with autologous stem cell support (for regimens expected to cause grade 3 or higher mucositis in most patients). Palifermin has no approved indication in head and neck cancer.
Limitations
The study was conducted only in patients with haematological malignancies receiving TBI-containing conditioning and autologous transplantation. The FDA label states that palifermin is not indicated for non-haematological tumours and that its safety and efficacy in these tumours have not been established; so these results cannot be extended to mucositis from chemoradiotherapy for head and neck cancer. The abstract gives no information on survival or disease relapse.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.