Yael Waknine

June 14, 2012

June 14, 2012 (Chicago, Illinois) — The new antibiotic fidaxomicin (Dificid, Optimer Pharmaceuticals) is superior to vancomycin in the treatment of cancer patients with Clostridium difficile–associated diarrhea (CDAD), according to research presented here at the 2012 Annual Meeting of the American Society of Clinical Oncology.

Fidaxomicin was approved by the US Food and Drug Administration last year for use in CDAD. The data presented at the meeting focused specifically on how the drug performs in cancer patients with CDAD.

C difficile infection, whether acquired from another patient during a long hospital stay or as an adverse effect of antimicrobial therapy that alters the gut flora, is a significant threat to cancer patients, who account for 16% of hospital-acquired CDAD cases.

"Most patients are on multiple antimicrobials when undergoing acute treatment for cancer, either to prevent or treat infection, and they are pretty susceptible to CDAD and other infections," Roy F. Chemaly, MD, MPH, FIDSA, FACP, told Medscape Medical News.

"Patients with leukemia and lymphoma and those undergoing stem cell transplants are at highest risk because they get much more aggressive chemotherapy and are immunosuppressed for a longer period of time," he added.

Dr. Chemaly is associate professor of medicine, director of the infection control section, and director of clinical virology at the University of Texas M.D. Anderson Cancer Center in Houston. Although Dr. Chemaly did not participate in the study, he is a paid consultant on the advisory board of Optimer Pharmaceuticals.

Complication Can Be Life-threatening

CDAD is a serious issue for cancer patients, said Kathleen Mullane, DO, PharmD, who presented the data. Dr. Mullane is associate professor of medicine and chief of clinical trials in the section of infectious diseases at the University of Chicago in Illinois.

"CDAD can be a life-threatening complication and a significant source of morbidity in patients who are already ill from their primary malignancy, as well as cancer therapy. When [cancer patients] have bad diarrhea, they're dehydrated and hospitalized; they can then acquire infections from the hospital and it frequently ends up being a vicious circle," Dr. Mullane told Medscape Medical News. The resulting delay or discontinuation of treatment is linked to a 2.7-fold increase in mortality risk.

"Having a drug that offers a lower relapse rate and can resolve the diarrhea more quickly is important for getting patients back on track with their cancer therapy," Dr. Mullane emphasized.

Comparison of Patients With and Without Cancer

Dr. Mullane and colleagues performed a subanalysis of data collected from 2 large phase 3 trials conducted by Optimer Pharmaceuticals for registration purposes.

The subanalysis focused on 1105 cancer patients with C difficile infection, 183 of whom had solid tumors, hematologic malignancies, or both.

The trial participants were randomly assigned to receive either fidaxomicin 200 mg twice daily (n = 539) or vancomycin 125 mg 4 times daily (n = 566) for 10 days.

Clinical end points included the resolution of diarrhea (3 or fewer unformed bowel movements per day, maintained until 2 days after the end of treatment), time to resolution of diarrhea, sustained response (clinical cure maintained for 4 weeks after treatment), and recurrence within 4 weeks (confirmed by a positive stool toxin test).

Results showed that cancer patients were less likely than patients without cancer to achieve a cure with either drug (92.2% vs 96.5%; P = .0130), more likely to experience prolonged diarrhea (time to resolution, 100 vs 55 hours; P = .0004), and more likely to relapse within 28 days (22.0% vs 19.9%; P = .57). Sustained response rates were 71.9% and 77.3%, respectively (P = .147).

"There appears to be no significant difference with respect to fidaxomicin cure rates between cancer patients and those who don't have cancer — both are over 90%. It appears that fidaxomicin takes away...the negative prognosis that cancer patients with CDAD have when exposed to traditional agents such as vancomycin," said Toyosi Odenike, MBBS, in an interview with Medscape Medical News.

Dr. Odenike is assistant professor of medicine in the section of hematology/oncology at the University of Chicago Comprehensive Cancer Center, and specializes in the treatment of adults with leukemia, chronic myeloproliferative and myelodysplastic diseases, and lymphoma. She was not involved in the clinical trials with fidaxomicin, and has no ties to Optimer Pharmaceuticals.

Comparison of Drugs in Cancer Patients

A subanalysis within the cancer population showed that fidaxomicin was superior to vancomycin on all counts.

Fidaxomicin was 5 times more likely than vancomycin to produce a clinical response (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.07 to 23.98; P = .041), and did so an average of 2 days sooner (74 vs 123 hours; P = .045).

Moreover, fidaxomicin was 3 times more likely to lead to a sustained response (OR, 3.22; 95% CI, 1.50 to 6.91; P =.003), and decreased disease recurrence by more than 50% (14.1% vs 30.0%; 95% CI, 0.16 to 0.89; P = .025). Those treated with vancomycin were 2.6 times more likely to experience relapse within 28 days (OR, 0.38; 95% CI, 0.16 to 0.89; = .025).

"Cancer patients are more susceptible than noncancer patients in terms of time to resolution of CDAD, so the shorter time observed with fidaxomicin is a big plus. Furthermore, CDAD recurrence is a significant issue, so the lower rate observed with fidaxomicin is also a plus," Dr. Odenike said.

"I strongly believe that fidaxomicin is a viable option for cancer patients with C difficile infection," Dr. Odenike explained, noting that the twice-daily rather than the 4-times-daily regimen is easier for patients to adhere to.

Although neither fidaxomicin nor vancomycin produced adverse events in the studies, fidaxomicin might be the safer option.

"The difference between oral fidaxomicin and oral or IV vancomycin is that the latter can have collateral damage in cancer patients, increasing their risk for the development of vancomycin-resistant Enterococcus," Dr. Chemaly noted.

Should Fidaxomicin Be Used Routinely?

Fidaxomicin is a relatively new drug; it has been available in the United States for just over a year.

"I am still using oral vancomycin in general, but I have used fidaxomicin in patients who have had not had the desired result with oral vancomycin and those who have recurrent diarrhea with vancomycin or metronidazole, which is a recognized therapy for CDAD," Dr. Odenike stated.

Dr. Chemaly is a proponent of first-line fidaxomicin therapy in certain patients.

"We developed a kind of algorithm and reserve first-line fidaxomicin for patients with multiple risk factors for recurrent infection, such as a very low white count, persistent diarrhea while on other treatments for C difficile infection, and other severe infection or colitis," Dr. Chemaly told Medscape Medical News.

One obstacle to the more widespread use of the new drug is cost. A 10-day course of fidaxomicin costs $2800, whereas generic vancomycin costs less than $300.

More outcome data are needed before the fidaxomicin is routinely used as initial therapy, Dr. Chemaly said.

2012 Annual Meeting of the American Society of Clinical Oncology (ASCO): Abstract 9067. Presented June 4, 2012.

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