Because evidence was unavailable from trials limited to outpatients, the ASCO Panel considered evidence from studies on inpatients or mixed populations, and the recommendatons are based on the summarized evidence and Panel members’ expert opinion.
Majority of randomly assigned patients in studies were hospitalized and treated for hematolgic malignancies. Taken together, evidence shows that systemically absorbed fluoroquinolones are more tolerable than other antibacterials investigated for prophylaxis in neutropenic oncology patients and are as efficisous yet more tolerable when used alone as when combined with other antibacterials active against Gram-positive organisms. Of note, use of a nonabsorbable antibacterial also significantly increased the number of microbiologically documented infections, Gram-negative infections, Gram-positive infections, bactermia, and overall adverse effects.
The Panel recommends use of an orally administered, systemically absorbed fluoroquinolone for antibacterial prophylaxis. Prophylaxis should be administered from the first day of the cytotoxic antineoplastic regimen unitl myeloid reconstitution. However, routine antibacterial prophylaxis should be avoided when expected duration of neutropenia is < 7 days, the severity is less than profound, and none of the risk factors list in table 1 in the post of risk evaluation and patient selection are present.
Also if antibacterial prophylaxis is given, a strategy to systematically monitor for fluoroquinolone resistance among Gram-negative bacilli in environments where fluoroquinolones are being deployed.
Results from clinical trial show that a majority of patients benefit from antifungal prophylaxis with orally absorbable or parenteral drugs versus controls receiving placebo, no treatment, or nonabsorbable oral drugs. These patients were at high risk for invasive Candida infection or aspergillosis resulting from long periods (≥ 7 days) of severe to profound neutropenia as a consequence of induction therapy for acute leukemia or HSCT.
The Panel recommends an orally administered triazole (fluconazole, itraconazole, posaconazole, or voriconazole) or an echinocandin administered parenterally (micafungin or caspofungin) for antifungal prophylaxis. Note that more trials of antifungal prophylaxis with more randomly assigned oncology patients at risk for IFIs have investigated fluconazole than any other orally absorbed or parenterally administered antifungal drug.
Meta-analysis found that TMP-SMX decreased the incidence of documented PCP, and PCP-related mortality versus controls receiving placebo, no treatment, or an antibacterial drug inactive against Pneumocystis. Also, additional meta-analyses showed no statistically significant differences between those randomly assigned to TMP-SMX and those randomly assigned to placebo or no treatment with respect to any adverse events or adverse event causing patients to discontinue treatment.
The Panel recommends using any of the published daily, twice per week, or three times per week schedules of TMP-SMX during the period of immunodeficiency: from engraftment until day 180 for those undergoing allogeneic HSCT, from initiation of induction therapy in acute lymphoblastic leukemia until completion of all antileukemic therapy. For patients who may be hypersensitive or unable to tolerate TMP-SMX for any reasons, alternatives may include dapsone, aerosolized pentamidine, or atovaquone.
Virus Reactivation Prophylaxis
It is recommended that an antiviral nucleoside analog with demonstrated activity against HBV as prophylaxis for those at substantial risk for reactivation of HBV infection. Studies reported statistically significant decreases in HBV reactivation and HBV-related hepatitis with lamivudine prophylaxis in patients at risk. The approach is to start therapy 1 week before chemotherapy begins and continuing for at least 6 months after chemotherapy ends.
HSV and VZV
It is recommend to use a nucleoside analog to prevent herpesvirus infection in those at risk from the initiation of cytotoxic therapy until myeloid reconstitution.
Finally, influenza immunization is recommended for all patients undergoing treatment for malignancy and for all family and household contacts. Trivalent inactivated vaccine should be used. In select circumstances after proven exposure of a susceptible patient with cancer, a neuraminidase inhibitor may be offered.