Phase II studies of BBR3464, a novel tri-nuclear platinum complex, in patients with gastric or gastro-oesophageal adenocarcinoma

Jodrell, Duncan I.; Evans, T.R. Jeffry; Steward, William P.; Cameron, David; Prendiville, Joseph A; Aschele, C.; Noberasco, Cristina; Lind, Michael; Carmichael, James; Dobbs, Nicola; Camboni, Gabriella; Gatti, Barbara; Braud, Filippo de

doi:10.1016/j.ejca.2004.04.032

Cited by 123 publications

(93 citation statements)

References 7 publications

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“…[35][36][37][38] Recent trials have also shown that these complexes may be degraded (and hence deactivated) by plasma proteins before they reach their intracellular target; possibly explaining the low activity of BBR3464 in phase II trials to date. [35][36][37][38] Recently, our group has identified a mechanism by which both the toxicity of these drugs could be decreased, and their degradation reduced within the human body. 39 Cucurbit[n]uril (Q[n]) is a barrel-shaped molecule, containing a hydrophobic cavity, formed by the acid catalysed condensation of glycoluril and formaldehyde (Fig.…”

Section: Introductionmentioning

confidence: 99%

Cucurbit[n]uril binding of platinum anticancer complexes

et al. 2006

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The encapsulation of cisplatin by cucurbit [7]uril (Q[7]) and multinuclear platinum complexes linked via a 4,4 -dipyrazolylmethane (dpzm) ligand by Q [7] and cucurbit [8] 4+ (tri-Pt) provide a barrier to the on and off movement of cucurbituril, resulting in binding kinetics that are slow on the NMR timescale for the metal complex. Although the dpzm ligand has relatively few rotamers, encapsulation by the larger Q[8] resulted in a more compact di-Pt conformation with each platinum centre retracted further into each Q[8] portal. Encapsulation of the hydrolysed forms of di-Pt and tri-Pt is considerably slower than for the corresponding Cl forms, presumably due to the high-energy cost of passing the +2 platinum centres through the cucurbituril portals. The results of this study suggest that cucurbiturils could be suitable hosts for the pharmacological delivery of multinuclear platinum complexes.

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Section: Introductionmentioning

confidence: 99%

Cucurbit[n]uril binding of platinum anticancer complexes

et al. 2006

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“…The lack of activity observed in the gastric and SCLC did not warrant further evaluation for these cancer types, 189,190 and although positive results were observed for some patients in the NSCLC (two objective responses and 11 PR from 33 patients) and ovarian (five PR from 46 patients) the drug has not moved into Phase III trials. The results of another Phase II study of BBR3464 in locally advanced or metastatic pancreatic cancer which started in 2001 under contract to Theradex R and the National Cancer Institute (USA) has yet to be reported.…”

Section: -192mentioning

confidence: 99%

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

et al. 2010

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

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“…12,13 In recent years, several Pt(II) compounds with trans configuration have been developed and reported to be active in vitro in different cancer cell lines, although none has entered phase III clinical trials. [14][15][16][17] Other platinum compounds with cis conformations have also been synthesized and studied as cancer therapeutics. Among these, satraplatin, an orally administered low toxicity platinum analog, demonstrated limited activity as a single agent in metastatic breast carcinoma and while still under investigation, failed in its initial development against prostate cancer;…”

Section: Resultsmentioning

confidence: 99%