Phase II trial of levocetirizine with capecitabine and bevacizumab to overcome the resistance of antiangiogenic therapies in refractory metastatic colorectal cancer

Background: Despite the clinical success of vascular endothelial growth factor (VEGF) blockade in metastatic colorectal cancers (mCRC), resistance to anti-angiogenic drugs invariably develops. IL-8 and other cytokines have been implicated in development of resistance to anti-angiogenic therapy. Levocetirizine is a second generation H1 antihistamine with anti-inflammatory and IL-8 suppression properties. We conducted a phase II trial combining levocetirizine with capecitabine and bevacizumab to potentially overcome anti-angiogenic therapy resistance in patients with refractory mCRC. Methods: This was a single-center open-label prospective trial in refractory mCRC patients. Treatment consisted of oral capecitabine 850 mg/m Results: Forty-seven patients were enrolled in the trial to have 36 evaluable patients. Arm A enrolled 23 patients and Arm B enrolled 24 patients. Fifty percent of patients had progressive disease and 62% of patients had stable disease in each arm as best response. There was no demonstrable difference in PFS between the two arms (log-rank test P=0.83). Median time to progression was 3.4 months in Arm A and 3.5 months in Arm B. Conclusions: Median PFS in the trial was comparable to and appeared to be better than other regimens used in the refractory setting (e.g., median PFS of 1.9 months for regorafenib). Cytokine measurement with IL-8 levels did not show any correlation with progression free survival but patients with stable disease showed overall lower levels of IL-8 as compared to patients with progressive disease in the cytokine analysis

Targeting GRPR in urological cancers--from basic research to clinical application

Gastrin releasing peptide (GRP) is a regulatory peptide that acts through its receptor (GRPR) to regulate physiological functions in various organs. GRPR is overexpressed in neoplastic cells of most prostate cancers and some renal cell cancers and in the tumoral vessels of urinary tract cancers. Thus, targeting these tumours with specifically designed GRP analogues has potential clinical application. Potent and specific radioactive, cytotoxic or nonradioactive GRP analogues have been designed and tested in various animal tumour models with the aim of receptor targeting for tumour diagnosis or therapy. All three categories of compound were found suitable for tumour targeting in animal models. The cytotoxic and nonradioactive GRP analogues have not yet shown convincing tumour-reducing effects in human trials; however, the first clinical studies of radioactive GRP analogues--both agonists and antagonists--suggest promising opportunities for both diagnostic tumour imaging and radiotherapy of prostate and other GRPR-expressing cancers