ONCOLOGY Vol 18 No 13

Lung cancer remains the leading cause of cancer death in Americanmen and women. Non–small-cell lung cancer (NSCLC) accountsfor 85% of these cases. Although surgery is the best curative approachfor resectable NSCLC, long-term survival for patients with operabledisease remains poor. More than half of patients who initially presentwith stage I to IIIA disease experience relapse of metastatic disease.Postoperative adjuvant therapy has been evaluated in several randomizedtrials, and provides a survival benefit. It appears reasonable tolook to induction chemotherapy, or preoperative chemotherapy, to providea similar improvement in survival with early treatment ofmicrometastatic disease. Multiple trials of induction therapy have beencarried out with encouraging results. The use of various induction regimenswith chemotherapy alone or chemotherapy combined with radiotherapyfor stage IIIA NSCLC is under investigation. Randomized trialsare under way to better define the role of induction therapy in themultimodality treatment of NSCLC.

Considering the significant morbidity and mortality associated withinvasive fungal infections in immunocompromised patients, it is particularlyimportant to make the diagnosis as early as possible and tomake best use of the available antifungal drugs for prophylaxis andtreatment. The newer antifungal drugs include the lipid products ofamphotericin B, such as amphotericin B lipid complex (ABLC) andliposomal amphotericin B; voriconazole (a triazole); and caspofungin(an echinocandin). ABLC and liposomal amphotericin B are as effectiveas amphotericin B deoxycholate but are less nephrotoxic; ABLC isprobably the drug of choice for zygomycosis. Voriconazole is approvedfor use in the treatment of invasive aspergillosis and may have a role inpreventing breakthrough fungal infections in patients with persistentfever and neutropenia. Caspofungin is effective against both invasiveaspergillosis and invasive candidiasis.

Candidiasis and aspergillosis are the most common fungal infectionsin hematopoietic stem cell transplant recipients and other hematology/oncology patients. Strategies for reducing the morbidity and mortalityassociated with these infections include antifungal prophylaxis,empiric therapy in patients with persistent fever and neutropenia, andpreemptive therapy. Antifungal therapies include amphotericin B deoxycholate,lipid formulations of amphotericin B, the triazoles (fluconazole,itraconazole, and voriconazole), and the echinocandins (caspofunginand the investigational agents micafungin and anidulafungin).Fluconazole is a reasonable choice for the treatment of invasive candidiasisif the patient has not previously received a triazole and theinstitution has a low incidence of triazole resistance. If resistance is aconcern, an echinocandin, such as caspofungin, is an appropriate option.Voriconazole may be the initial choice in most patients with invasiveaspergillosis. If patients are intolerant of or refractory to conventionaltherapy, effective alternatives include a lipid formulation of amphotericinB or an echinocandin.

Combination therapy with amphotericin B and flucytosine is consideredto be the treatment of choice for cryptococcal infections. However,for other infections and combinations of antifungal infections,the data are less clear-cut. The concurrent use of amphotericin B withan azole has elicited controversy, given the potential of antimicrobialantagonism. The results of one recent candidemia study suggest thatthe potential antagonism may not be an issue; the combination of amphotericinB and fluconazole provided more effective clearance of Candidafrom the bloodstream than did fluconazole used alone. Several invitro and animal studies have shown antagonism between the azolesand amphotericin B for aspergillosis. However, introduction of the newclass of agents that target β-glucan synthase (echinocandins) has invigoratedthe prospects of combination therapy. The echinocandins andpolyenes are not antagonistic, and there is evidence that theechinocandins may provide additive to synergistic activity in combinationwith triazoles. For patients whose aspergillosis is progressing despitemonotherapy, the addition of a second agent, such as anechinocandin, may be reasonable.