Hyaluronan-Irinotecan improves progression-free survival in 5-fluorouracil refractory patients with metastatic colorectal cancer: a randomized phase II trial

Abstract

Further studies are required to define the safety of the formulation of irinotecan with HA. While this study was not adequately powered to demonstrate survival differences, these phase II data indicated HA-Irinotecan to be a promising therapy demonstrating improved efficacy compared to irinotecan-alone.

Versican induces a pro-metastatic ovarian cancer cell behavior which can be inhibited by small hyaluronan oligosaccharides

“…Intra peritoneal administration of a bioconjugate of HA and paclitaxel was well tolerated and significantly decreased growth human ovarian cancer xenografts in SCID mice compared with paclitaxel alone [73,74]. More recently phase I and phase II clinical trials have demonstrated that HA and the chemotherapy drug irinotecan can be safely administered together to patients with metastatic colon cancer and improve progression free survival [75,76]. We envisage that HA oligomers could be administered intra-peritoneally Fig.…”

Hyaluronan drug delivery systems are promising for cancer therapy because of their selective attachment, enhanced uptake, and superior efficacy

“…In addition, the control rate of the disease has increased from 46% to 76%, respectively [88]. Patients treated with hyaluronan-irinotecan mixture are also less likely to have a progressive disease (21% versus 41%) after two treatment cycles [88]. Furthermore, 34% of the patients have completed eight cycles in contrast to 14% of the patients who received Irinotecan [88].…”

“…Results from phase II clinical trials show reduced side effects such as diarrhea in patients treated with hyaluronan-irinotecan mixture as compared with Irinotecan only. In addition, the control rate of the disease has increased from 46% to 76%, respectively [88]. Patients treated with hyaluronan-irinotecan mixture are also less likely to have a progressive disease (21% versus 41%) after two treatment cycles [88].…”

CD44 as a drug delivery target in human cancers: where are we now?

“…It should also be noted that in the Phase II trial, the experimental arm received an average of six cycles of treatment versus only two for the standard therapy arm [7]; one might speculate that this alone could significantly contribute to the improved PFS observed in the former arm, a result not sustained in the Phase III trial, wherein 8 months of treatment were to be administered to both arms.…”

“…Fatal complications of CD44v6-MAb-Mertansineadministration, such as toxic epidermal necrolysis, caused early termination of clinical development of these MAbs [4,5] On the other hand, a drug delivery approach based on the HA--CD44 axis, wherein Irinotecan was enveloped non-covalently within a domain of~750 kDa HA, successfully passed Phase I toxicity assessments [6], which led to further clinical studies to investigate the utility of this axis. A Phase II study from Australia demonstrated improved progression-free survival (PFS) in metastatic colorectal cancer (CRC) patients treated with HA--Irinotecan compared to the arm with free Irinotecan (5.2 vs 2.4 months, respectively; p = 0.007), and thus warranted an expanded, multicenter Phase III study [7]. This trial enrolled metastatic CRC patients who were Irinotecan naïve but were candidates for secondand third-line chemotherapy.…”