The ACT II trial from the UK which also analyzed if cisplatin could replace MMC showed that there was no difference in clinical complete response or OS with either MMC or cisplatin (34). The ACT II trial also studied if maintenance therapy after definitive chemoradiation would be of benefit and reported that maintenance therapy did not improve overall survival or recurrence Inhibitors,research,lifescience,medical free survival. Follow-up for the ACT II trial is only at 3 yrs so further study is needed to determine if cisplatin could substitute for MMC (34). Currently concurrent 5FU + MMC

with radiation is still the standard of care. Treatment breaks due to toxicity lead to prolonged RT treatment duration and at times patients are unable to complete the planned RT. A

report from Boston University Medical Center demonstrated that RT dose (≥ 54Gy) was significantly associated with local control and overall survival and treatment time less than 40 days also showed a trend toward Inhibitors,research,lifescience,medical improved outcome (35). Other studies confirmed that greater overall treatment time was associated with worse outcomes and local failure (36). This is a clinical example of accelerated repopulation of residual tumor clonagens, in all likelihood (37). Roohipour et al 2008 in a multivariate analysis of 131 patients with anal squamous cell carcinoma showed the inability to complete definitive RT and disease stage at diagnosis were both predictive of relapse free survival (38). A Inhibitors,research,lifescience,medical recent analysis of 2 RTOG trials showed that for every 2 weeks of treatment interruption Inhibitors,research,lifescience,medical there was a 9.4% increase in the hazard ratio for colostomy failure

(39). The success of sphincter sparing treatment is in part dependent upon getting the patient through treatment without interruptions for treatment side effects. It FK228 should be noted that during the development of the aforementioned prospective trials, there was a consensus among those designing the studies before the HAART era that an unfavorable therapeutic ratio would be seen in HIV+ patients. Hence this study population was heretofore Inhibitors,research,lifescience,medical excluded from participation onto such studies. HIV positive patients and treatment for anal cancer There have been concerns that HIV+ patients have increased toxicity and tolerate treatment less than the HIV negative Rolziracetam patient. As a result physician bias has trended toward reducing the dose/amount of concurrent chemoradiation treatment for HIV+ patients for fear of causing unacceptable toxicity and a suboptimal therapeutic ratio. Such changes in practice can lead to treatment failures in the HIV+ population. Retrospective studies have been conducted to address such concerns. Early reports likely contributed to the perception that HIV+ patients do not tolerate aggressive combined modality treatment. Peddada et al (1997) in a limited study demonstrated that 8 HIV+ patients with anal cancer could be treated with concurrent 5FU/MMC but used a lower dose of RT, 30Gy instead of the standard of care > 50Gy (40).