We attempted to determine whether the administration of aspirin or ursodeoxycholic acid during loss of weight could prevent the development of lithogenic changes in bile and the formation of gallstones. Sixty-eight obese subjects without gallstones who were entered in a program (520 kcal per day) to lose weight were randomly assigned to receive ursodeoxycholic acid (1200 mg per day), aspirin (1300 mg per day), or placebo in double-blind fashion for up to 16 weeks. At entry, at four weeks of treatment, and at three weeks after the completion of treatment, the subjects underwent ultrasonography to detect gallstones and duodenal drainage of bile to detect cholesterol crystals and to determine the bile saturation index and glycoprotein concentration. No gallstones or cholesterol crystals formed in the patients treated with ursodeoxycholic acid. Among the patients given placebo, gallstones formed in five (P less than 0.05 vs. ursodeoxycholic acid) and cholesterol crystals in six (P less than 0.001 vs. ursodeoxycholic acid); among those given aspirin, gallstones formed in two and cholesterol crystals in one (no significant difference from ursodeoxycholic acid treatment). By the fourth week, the bile saturation index increased in the placebo group (from 1.07 +/- 0.26 to 1.29 +/- 0.27; P less than 0.001), decreased in the ursodeoxycholic acid group (from 1.11 +/- 0.34 to 0.91 +/- 0.24; P less than 0.001), and did not change significantly in the aspirin group. The concentration of glycoprotein in bile increased in the placebo group (27.9 +/- 14.5 percent; P less than 0.001) but did not change significantly in the groups treated with ursodeoxycholic acid or aspirin. We conclude that ursodeoxycholic acid prevents lithogenic changes in bile and the formation of gallstones in obese subjects during loss of weight.

Biologics play a key role in cancer treatment and are principal components of many therapeutic regimens. However, they require complex manufacturing processes, resulting in high cost and occasional shortages in supply. The cost of biologics limits accessibility of cancer treatment for many patients. Effective and affordable cancer therapies are needed globally, more so in developing countries, where health care resources can be limited. Biosimilars, which have biologic activity comparable to their corresponding reference drugs and are often more cost effective, have the potential to enhance treatment accessibility for patients and provide alternatives for decision makers (ie, prescribers, regulators, payers, policymakers, and drug developers). Impending patent expirations of several oncology biologics have opened up a vista for the development of corresponding biosimilars. Several countries have implemented abbreviated pathways for approval of biosimilars; however, challenges to their effective use persist. Some of these include designing appropriate clinical trials for assessing biosimilarity, extrapolation of indications, immunogenicity, interchangeability with the reference drug, lack of awareness and possibly acceptance among health care providers, and potential political barriers. In this review, we discuss the potential role and impact of biosimilars in oncology and the challenges related to their adoption and use. We also review the safety and efficacy of some of the widely used biosimilars in oncology and other therapeutic areas (eg, bevacizumab, darbepoetin, filgrastim, rituximab, and trastuzumab).