Anal cancer: is neoadjuvant cisplatin chemotherapy or chemoradiotherapy friend or foe?

This Practice Point commentary discusses the findings of the Intergroup RTOG 98-11 trial, which aimed to investigate both the potential role of cisplatin as neoadjuvant chemotherapy, and also its role concurrently in combination with radiotherapy, for anal-canal carcinoma. Although chemoradiotherapy has had an important effect on the treatment of anal cancer, and allows preservation of anorectal function with survival rates similar to or better than those of surgical treatment, overall survival rates for advanced tumors are still in the region of 50-60% at 5 years. A strong theoretical rationale for cisplatin-based treatment in anal cancer exists; several phase II trials have demonstrated a high response rate with reduced colostomy rates. The Intergroup results are disappointing in that neoadjuvant chemotherapy with cisplatin and 5-fluorouracil, followed by cisplatin-based chemoradiotherapy did not improve overall survival, disease-free survival and locoregional control when compared with the standard treatment of combined 5-fluorouracil and mitomycin chemoradiotherapy.     

The present and future of peptide vaccines for cancer: single or multiple, long or short, alone or in combination?

Peptide vaccines incorporate one or more short or long amino acid sequences as tumor antigens, combined with a vaccine adjuvant. Thus, they fall broadly into the category of defined antigen vaccines, along with vaccines using protein, protein subunits, DNA, or RNA. They remain one of the most immunogenic approaches, based on measures of T-cell response in the blood or in draining lymph nodes. However, existing peptide vaccines have had limited success at inducing clinical tumor regressions, despite reliable induction of T-cell responses. Several new developments offer promise for improving peptide vaccines, including use of long peptides, optimization of adjuvants including toll-like receptor agonists, and combination with systemic therapies that may reduce tumor-associated immune dysfunction, such as blockade of PD-1/PD-L1 interactions. To apply these new approaches optimally, it will be critical to study their effects in the context of defined antigens, for which peptide vaccines are optimal.     

Phytoestrogens: perpetrators or protectors?

Phytoestrogens are estrogen-like substances produced by plants that account for some of the constituents present in vegetation that may be responsible for the health benefits of a diet rich in fruit and vegetables. Phytoestrogens have a plethora of different actions that they are capable of exerting on cellular metabolism. This review will focus on some of the major non-estrogen receptor-mediated cellular effects used by phytoestrogens and will draw attention to the fact that while they may have a number of beneficial effects, particularly in offering a protective effect against some hormone-dependent cancers, such as breast and prostate cancer, they may also have possible unfavorable effects by interfering with the functioning of normal cellular activities such as receptor-mediated signal transduction and DNA replication, as well as being genotoxic, mutagenic and promoting the proliferation of some cancer cells.