Tolerability of paclitaxel/carboplatin (PCb) in solid tumor patients (pts) infected with HIV.

Abstract

e14077 Background: Although cancer has long been a recognized hallmark of the HIV epidemic, the preservation of immunologic health with modern antiretroviral therapy (ART) and aging has resulted in a population increasingly susceptible to cancers not traditionally associated with advancing immunosuppression. Several of these cancers (including lung, anal and head & neck) are seen in excess compared to the background population. Defining tolerability of standard treatments and analyzing potential interactions between ART and chemotherapy provides evidence necessary to mitigate treatment disparities. Methods: We conducted a study to evaluate the tolerability of PCb in HIV+ cancer pts. AMC-078 (NCT01249443), originally designed as a phase I of vorinostat in combination with fixed doses of P (at 175mg/m2) and Cb (AUC 6) every 3 weeks, was amended to study pts treated with PCb alone after phase III testing in the background population was negative for the combination in lung cancer. Eligibility criteria: PS ≤ 2, advanced solid tumor and normal organ function, including CD4 count > 100 cells/mcL on stable ART. Up to 6 cycles of PCb were permitted. Clinically significant adverse events (AE) in prior cycles were managed by dose reductions. Results: 17 pts (10M/7F; median CD4, 389/mcL) were accrued, including lung (9) and anal (3) cancers; 8 pts had ritonavir (potent CYP inhibitor)-containing ART. 65 PCb cycles were administered to 16 evaluable pts, for a mean of 4+ cycles/pt; only 2 pts were treated with vorinostat. AE of special interest included ≥G3 (febrile) neutropenia and ≥ G2 neuropathy, below. 4 pts had partial responses (3 confirmed). Pharmacokinetic analyses (7 pts) are pending. Conclusions: PCb has similar toxicity profile in fit pts with HIV infection. No signal for worse myelosuppression or neuropathy was observed by ART regimen. Routine use of GCSF or empiric dose reduction for presumed risk is unjustified. Results support standard cancer treatment for this underserved population. Clinical trial information: NCT01249443. [Table: see text]