The status of platinum anticancer drugs in the clinic and in clinical trials

Since its approval in 1979 cisplatin has become an important component in chemotherapy regimes for the treatment of ovarian, testicular, lung and bladder cancers, as well as lymphomas, myelomas and melanoma. Unfortunately its continued use is greatly limited by severe dose limiting side effects and intrinsic or acquired drug resistance. Over the last 30 years, 23 other platinum-based drugs have entered clinical trials with only two (carboplatin and oxaliplatin) of these gaining international marketing approval, and another three (nedaplatin, lobaplatin and heptaplatin) gaining approval in individual nations. During this time there have been more failures than successes with the development of 14 drugs being halted during clinical trials. Currently there are four drugs in the various phases of clinical trial (satraplatin, picoplatin, LipoplatinTM and ProLindacTM). No new small molecule platinum drug has entered clinical trials since 1999 which is representative of a shift in focus away from drug design and towards drug delivery in the last decade. In this perspective article we update the status of platinum anticancer drugs currently approved for use, those undergoing clinical trials and those discontinued during clinical trials, and discuss the results in the context of where we believe the field will develop over the next decade

Bifurcation analysis of a semiconductor laser subject to non-instantaneous phase-conjugate feedback

We consider how the behaviour of a semiconductor laser subject to phase-conjugate feedback depends on the interaction time of the phase-conjugating mirror. We employ continuation techniques to show how the bifurcation diagram in the plane of feedback strength versus pump current changes as the interaction time of the mirror is increased. This shows that for interaction times below 0.1 ns the assumption of instantaneous feedback is justified. On the other hand. we show that increasingly larger interaction times lead to considerable changes in the size and qualitative structure of the locking region. Our study provides a more global view of the suppression of complicated and chaotic dynamics. (C) 2003 Elsevier B.V. All rights reserved