Despite greater toxicity, the use of MMC in a definitive CR regimen for anal cancer is justified, particularly in patients with large primary tumors. Salvage CR should be attempted in patients with residual disease following definitive CR before resorting to radical surgery.

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A B S T R A C T PurposeTo determine whether increased duration of radiation therapy (RT) and overall treatment (RX) time has a detrimental effect in anal cancer. Patients and MethodsData from Radiation Therapy Oncology Group (RTOG) 87-04 and RTOG 98-11 trials were combined to form three treatment groups: RT/fluorouracil (FU)/mitomycin (n ϭ 472), RT/FU/ cisplatin (n ϭ 320), and RT/FU (n ϭ 145). Cox proportional hazards models were used with the following variables: RT duration, RT intensity, RX duration, treatment group, age, sex, Karnofsky performance score (KPS), T stage, N stage, and RT dose. ResultsIn the univariate analysis, there was a significant association between RX duration and colostomy failure (CF; hazard ratio [HR] ϭ 1.51; 95% CI, 1.07 to 2.14; P ϭ .02), local failure (HR ϭ 1.52; 95% CI, 1.14 to 2.03; P ϭ .005), locoregional failure (HR ϭ 1.51; 95% CI, 1.15 to 1.98; P ϭ .003), and time to failure (HR ϭ 1.40; 95% CI, 1.10 to 1.79; P ϭ .007). The significance of RX duration was maintained after adjusting for treatment group. In multivariate modeling there was a trend toward an association between RX duration and CF (HR ϭ 1.57; 95% CI, 0.98 to 2.50; P ϭ .06) and a statistically significant association with local failure (HR ϭ 1.96; 95% CI, 1.34 to 2.87; P ϭ .0006). Age, sex, KPS, T stage, N stage, and RT dose, but not RT duration, RT intensity, or RX duration, were found to be statistically significant predictors of OS and colostomyfree survival. ConclusionTotal treatment time, but not duration of radiation therapy, seems to have a detrimental effect on local failure and colostomy rate in anal cancer. Induction chemotherapy may contribute to local failure by increasing total treatment time.

Purpose: Patients with monoclonal gammopathy of undetermined significance (MGUS) have increased rates of bone resorption, osteopenia, osteoporosis, and risk of fractures. This study was undertaken to determine the efficacy and safety of zoledronic acid for patients with MGUS and enhanced bone loss. Experimental Design: In this phase II open-label study, 54 patients with MGUS and osteopenia or osteoporosis were administered zoledronic acid 4 mg i.v. at 0, 6, and 12 months. The primary efficacy end point was bone mineral density, assessed using a dual-energy X-ray absorptiometry scan in the lumbar (L)-spine done at screening and at 13 months (1 month after the final zoledronic acid infusion). Results: At study end for all patients (N = 54), L-spineT-scores improved by a median of +0.27 (range, -0.38 to +3.91), corresponding to a median increase in bone mineral density of +15.0%(range, -18.0% to +1,140.0%; P < 0.0001). Hip T-scores improved by a median of +0.10 (range, -2.40 to +2.03), corresponding to a median increase of +6.0% (range, -350.0% to +165.0%). During the study, no new fractures, osteonecrosis of the jaw, or significant renal adverse events were reported. Conclusions: Zoledronic acid administered i.v. at a dosage of 4 mg every 6 months for three doses total was well-tolerated and substantially improved bone mineral density for patients with MGUS and bone loss. Zoledronic acid may be effective for the prevention of new fractures in this high-risk population.

SummaryWe assessed the safety and efficacy of melphalan, arsenic trioxide (ATO) and ascorbic acid (AA) (MAC) combination therapy for patients with multiple myeloma (MM) who failed more than two different prior regimens. Patients received melphalan (0AE1 mg/kg p.o.), ATO (0AE25 mg/kg i.v.) and AA (1 g i.v) on days 1-4 of week 1, ATO and AA twice weekly during weeks 2-5 and no treatment during week 6 of cycle 1; during cycles 2-6, the schedule remained the same except ATO and AA were given twice weekly in week 1. Objective responses occurred in 31 of 65 (48%) patients, including two complete, 15 partial and 14 minor responses. Median progression-free survival and overall survival were 7 and 19 months respectively. Twenty-two patients had elevated serum creatinine levels (SCr) at baseline, and 18 of 22 (82%) showed decreased SCr levels during treatment. Specific grade 3/4 haematological (3%) or cardiac adverse events occurred infrequently. Frequent grade 3/4 non-haematological adverse events included fever/chills (15%), pain (8%) and fatigue (6%). This steroid-free regimen was effective and well tolerated in this heavily pretreated group. These results indicate that the MAC regimen is a new therapeutic option for patients with relapsed or refractory MM.