New ASCO guidelines change recommendations for amifostine, add section on palifermin

In the first update to recommendations about the use of chemotherapy and radiation therapy protective agents in six years, the American Society of Clinical Oncology no longer supports the use of amifostine for the prevention of a number of potential side effects.

ASCO has also created guidelines on palifermin (Kepivance, Amgen), a recombinant keratinocyte growth factor approved by the FDA in 2005. The drug is a prophylactic against severe mucositis associated with hematopoietic stem-cell transplantation.

The updated guidelines were published in the November issue of The Journal of Clinical Oncology. ASCO updates its recommendations when new and relevant information becomes available.

Small updates

The committee that wrote the guidelines made one change to recommendations regarding the use of dexrazoxane, deleting a statement about use of the drug in patients assigned to high-dose anthracycline therapy. The authors wrote that there was no new data about using the drug in that setting or regarding the clinical use of high-dose anthracyclines.

Guidelines regarding the use of mesna, a chemoprotectant used in conjunction with ifosfamide, were unchanged because no new data on the drug has been released.

“Mesna has a fairly isolated niche,” said Martee L. Hensley, MD, co-chair of the committee that wrote the new guidelines and an associate professor of medicine at Memorial Sloan-Kettering Cancer Center. “Mesna is quite effective at reducing [hemorrhagic cystitis] and most physicians who use ifosfamide routinely do use mesna as a chemoprotectant.”

ASCO dropped recommendations for the use of amifostine for a range of potential side effects including prevention of platinum-based neurotoxicity or otoxicity, protection against thrombocytopenia in patients receiving chemotherapy or radiotherapy and prevention of neuropathy associated with paclitaxel.

Hensley said that in many cases, data supporting the use of amifostine were not strong enough to continue recommending the drug.

“In some cases, this is not because we’re sure the drug is ineffective, but rather the trial design to support its use was not sufficiently strong to show us amifostine was clearly efficacious in those areas,” she said. “The data for amifostine as a protectant are somewhat limited. We try to base our recommendations on, ideally, randomized, placebo-controlled trials.”

Hensley went on to say that because amifostine is used to prevent somewhat subjective conditions such as the impact of mucositis on quality of life, the committee feels it is crucial that the drug is evaluated in placebo-controlled trials.

“Perhaps particularly in a guideline where the endpoints can be difficult to measure, then the use of a placebo in the trial design is particularly important because the assessment of whether the protectant is working or not is relatively subjective,” she said. “For the chemo- and radio-protectant guidelines, particularly when the assessment or the endpoint is somewhat subjective, it is often critical that the trials are placebo-controlled.

“In contradistinction, the data for palifermin are much stronger and we do recommend palifermin for patients undergoing stem-cell transplantation where the preparative regimen includes total body irradiation.”

Use of palifermin

The committee recommends palifermin for patients undergoing autologous stem-cell transplantation for a hematologic malignancy with a TBI-conditioning regimen and for patients undergoing myeloablative allogenic hematopoietic stem-cell transplantation with a TBI-conditioning regimen. The authors determined there was not enough evidence to support administering palifermin to patients undergoing a conditioning regimen of chemotherapy alone.

The committee also decided there was not enough data to support the use of palifermin in non–stem-cell transplantation settings or for treating solid tumors.

Hensley said the guidelines serve as both an aid to clinicians and to highlight potential areas for additional study.

“Obviously, we recognize there are all kinds of individualized situations out there that might lead a clinician to differ from the guidelines,” she said. “They are meant to be used as a tool by clinicians to help them in their choices of how to treat patients.

“From the other side, in terms of further research, we hope the guideline in some ways does highlight places where there remains a clinical need for improvement and that well-designed clinical trials will be done to help us prove or disprove the efficacy of these drugs. If the drugs we have in our armamentarium so far are not particularly efficacious, maybe that will spur research for better chemo- and radio-protectants.” – by Jason Harris

J Clin Oncol. 2008;doi:10.1200/JCO.2008.17.2627.