Rescue chemotherapy using multidrug chronomodulated hepatic arterial infusion for patients with heavily pretreated metastatic colorectal cancer

Abstract

Original carbohydrate‐based acrylamides bearing one azide group in C‐2 or C‐6 position namely, 2‐[(2‐deoxy‐2‐azido‐α‐D‐mannopyranosyloxy)ethanamido]‐ethyl acrylamide (II) and 2‐[(6‐deoxy‐6‐azido‐α‐D‐glucopyranosyloxy)ethanamido]‐ethyl acrylamide (III), and their azide‐free analogue, 2‐[(α‐D‐glucopyranosyloxy)ethanamido]‐ethyl acrylamide (I), have been designed. Whereas the reversible addition fragmentation chain transfer (RAFT) process ensured the preparation of well‐defined glycopolymers from I, the polymerization of monomers II and III proved to be challenging at temperatures compatible with a thermally initiated radical process, due to the presumed concomitant 1,3‐cycloaddition reactions between the azide and the acrylamide moieties. In contrast to III, for which no polymer could be obtained under any conditions, performing the RAFT polymerization of II at 30 °C clearly favored the radical polymerization and conferred a controlled character to the process, affording well‐defined azide‐functionalized glycopolymers and block copolymers. The presence of numerous azide moieties was finally exploited to introduce carbohydrates onto the glycopolymer backbone through copper catalyzed azide‐alkyne cycloaddition. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Early tumour response as a survival predictor in previously- treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer

“…This mechanism should thus both accelerate and increase magnitude of LM shrinkage [19]. A prior salvage study offered an initial proof of this therapeutic concept in 29 patients receiving chronomodulated HAI of irinotecan, 5-fluorouracil and oxaliplatin for unresectable liver metastases, following failure of a median of four prior systemic chemotherapy protocols [21]. OPTILIV further combined chronomodulated or conventional triplet HAI delivery with intravenous cetuximab in 64 patients with prior 15/19 exposure to one to three chemotherapy protocols for extensive LM from KRAS wt colorectal cancer [17].…”

Hepatic arterial infusion in colorectal carcinoma: is anatomical targeting still relevant in an era of molecularly targeted therapy?

“…Partial response was observed in 10 patients (35%) and resection could be performed in 4 patients. Median progression-free survival and overall survival were 5 months and 18 months, respectively 72 . Chen et al reported on HAI of oxaliplatin, irinotecan and doxifluridine in combination with systemic administration of doxifluridine and leucovorin in 32 patients 73 .…”

“…Systemic administration of irinotecan was also studied in combination with HAI of floxuridine in 39 heavily pretreated patients resulting in 44% response rate with median survival of 20 months 71 . HAI of the combination of oxaliplatin, irinotecan and 5-fluorouracil administered in a chronomodulated regimen was studied in 29 heavily pretreated metastatic colorectal carcinoma patients 72 . Partial response was observed in 10 patients (35%) and resection could be performed in 4 patients.…”

“…Again, the response and resection rates were higher in patients treated in the first line. Liver resections were also reported after HAI administered as second or third line of therapy of colorectal carcinoma liver metastases 47,57,71,72 . HAI has also been successfully combined with RFA (ref.…”

“…Relatively low efficacy has been reported in studies using fluoropyrimidine monotherapy 115 , but high response rate and prolonged survival have been reported in patients treated with combined regimens [55][56][57]72 . Obviously, the patient selection plays a significant role in the second or higher line therapy setting, and prolonged survival has been documented in individual patients, even when using HAI of drugs administered earlier in the course of therapy 72 . Even at the time when HAI offered the highest disease control rates of all available therapies, the utilization of this approach differed markedly among institutions.…”