Repeated biopsies in evaluation of therapeutic effects in prostate carcinoma

Abstract

Histological evaluation of mitotic and apoptotic index, Ki67, and p53 expression in repeated biopsies contributes to predicting the value of the actual treatment and may be useful to institute alterations in therapy.

Inhibitors Targeting Mitosis: Tales of How Great Drugs against a Promising Target Were Brought Down by a Flawed Rationale

“…This means that at any one time, only a very small percentage of tumor cells are undergoing mitosis. Indeed, the mean mitotic index in a variety of tumor types has been shown to be <1% (19,20). Additionally, the mean labeling index measured by radiolabeled imaging [e.g., tritiated thymidine ([3H]-TdR)] was only a few percent of the tumor (21).…”

Toward better early-phase brain tumor clinical trials: A reappraisal of current methods and proposals for future strategies

“…In contrast to cytotoxic agents, each of these agents typically attacks a speci c molecular target and the effects of the agent can be determined at the molecular level. This suggests that the end points of clinical trials evaluating the new targeted agents can be direct: the speci c molecular effect of the agent on the tumor can be measured (Dowlati et al, 2001;Eisenhauer, 1998;Gelmon et al, 1999;Mauro et al, 2002;Spiro et al, 1999;Szende et al, 2001;Plecha et al, 1997). For example, in the evaluation of receptor tyrosine kinase inhibitors (such as STI571), direct measurements of receptor activity (such as PDGFR phosphorylation) within tumor specimens can be made.…”

“…In this context, the success of a molecularbased therapeutic approach rests on proving that an anticancer agent is capable of altering the molecular target against which it was designed. Obtaining such a proof will require that clinical trials of brain tumor therapies incorporate measurements of the molecular effects of the agent on the tumor (Dowlati et al, 2001;Eisenhauer, 1998;Gelmon et al, 1999;Spiro et al, 1999;Szende et al, 2001;Plecha et al, 1997).…”

“…This correlation will be required to fully determine the activity of a new agent and its potential use in combination with other agents. Although awareness has increased for the need to integrate molecular analyses of tumor specimens into classic phase I and phase II trials, the incorporation of these end points into brain tumor trials has lagged behind other tumor types (Dowlati et al, 2001;Eisenhauer, 1998;Gelmon et al, 1999;Mendel et al, 2000;Plecha et al, 1997;Sabiers et al, 1993;Spiro et al, 1999;Szende et al, 2001). Understanding the requirements of these types of studies and the impact on trial design may help to speed the development of molecular-based clinical trials for brain tumors.…”

“…Tissue can be acquired either by stereotactic biopsy or open craniotomy. Taking serial biopsies before and after treatment is most desirable (Dowlati et al, 2001;Plecha et al, 1997;Szende et al, 2001), but may not be feasible for many brain tumor trials. Another potential limitation is the typically small amount of tissue obtained by needle biopsies, which may not provide an adequate sample for analysis given the heterogeneity of gliomas.…”