Panel proposes consensus definition of cisplatin ineligibility criteria

ORLANDO — Analysis of survey responses from 65 medical oncologists from five countries yielded a working definition of cisplatin eligibility criteria that may be useful for categorizing patients with urothelial carcinoma, according to findings presented at the 2011 Genitourinary Symposium.

Matthew D. Galsky, MD, assistant professor of hematology, medical oncology and urology at Mount Sinai School of Medicine, said there is tremendous variability in criteria determining which urothelial carcinoma patients are considered unfit for cisplatin therapy.

“A uniform definition of ‘unfit’ will lead to more uniform trials and better outcomes in this subset,” Galsky said, noting that definitions vary from the “pick-and-choose” variety — in which a patient is determined unfit if he fulfills certain criteria from a predetermined list — to more traditional lists of inclusion and exclusion criteria.

The current study employed a threefold approach. “First, we surveyed 120 [genitourinary] medical oncologists from five countries,” he said. “We then reviewed the literature for cisplatin ineligibility criteria in solid tumors. Then the panel reconciled the survey results with the available literature and generated a consensus definition.”

Sixty-five of the 120 clinicians surveyed responded. Fourteen of 236 potentially relevant articles were analyzed. “Within the 14 trials we evaluated, there was variability in the definition of unfit,” Galsky said. “These studies employed a variety of thresholds for performance status, creatinine levels and comorbidities.”

A creatinine clearance rate of less than 60 mL/minute was the most commonly reported criteria, followed by ECOG performance status of at least 2. “The majority of clinicians, around 82%, said that age should not be included in this definition,” Galsky said. “Neuropathy, hearing loss and heart failure were other commonly reported criteria.”

Reconciling the survey results with the available literature, the panel recommended the following criteria for the definition of unfit for cisplatin-based chemotherapy in clinical trials involving metastatic urothelial carcinoma patients:

• ECOG performance status of 2 and/or;
• Creatinine clearance of less than 60 mL/minute and/or;
• Common Terminology Criteria for Adverse Events of at least grade 2 hearing loss and/or;
• Common Terminology Criteria for Adverse Events of at least grade 2 neuropathy.

“We are hoping this simple, concise definition can improve on the substantial heterogeneity that exists in the definition of cisplatin ineligibility,” Galsky said.

For more information:

• Galsky MD. #238. Presented at: 2011 Genitourinary Symposium; Feb. 15-19, 2011; Orlando, Fla.

Disclosure: Dr. Galsky reports no relevant financial disclosures.

Maha Hussain

Cisplatin has been around for a long time. Much of what we know about the feasibility of administering the drug and to which patients has been based on earlier single agent and combination clinical trials in a variety of cancers. Clinicians also use their medical judgment in selecting patients for cisplatin therapy. The drug is associated with a variety of side effects, including nephrotoxicity, ototoxicity and neuropathy, among other side effects. The need for saline hydration requires adequate cardiac function. Therefore, patients with significant comorbidities or older patients, for example, do not tolerate it well.

Galsky and colleagues have attempted to codify the somewhat diverse criteria for suitability to receive cisplatin employed by clinicians in the context of urothelial carcinoma. They attempted to define a consensus set of potential criteria that can be used in everyday practice or in the context of clinical trials so that we are comparing apples to apples. I applaud the effort of the investigators. However, for the most part, their results are generally consistent with what is used.

That said, I must note the importance of integrating the science and the art of medicine. Although consensus criteria are useful as a guideline, they do not replace the physician’s assessment at an individual patient level, taking into account other factors that can impact the decision and the objectives of therapy.

– Maha Hussain, MD, FACP

HemOnc Today Editorial Board member

Disclosure: Dr. Hussain reports no relevant financial disclosures.