Sustained complete response to erlotinib in squamous cell carcinoma of the head and neck: A case report.

BACKGROUND: Squamous cell carcinoma of head and neck (SCCHN) is the fifth most common cancer worldwide. Inhibition of epidermal growth factor receptor signaling has been shown to be a critical component of therapeutic option. Herein, we report a case of durable complete response to erlotinib. CASE SUMMARY: An 81-year-old Caucasian male who presented with metastatic poorly differentiated squamous cell carcinoma of right cervical lymph nodes (levels 2 and 3). Imaging studies including (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and contrast-enhanced CT scan of neck and chest did not reveal any other disease elsewhere. Panendoscopic examination with random biopsy did not reveal malignant lesion in nasopharynx, oropharynx, and larynx. He underwent modified neck dissection and postoperative radiation. Within 2 mo after completion of radiation, he developed local recurrence at right neck, which was surgically removed. Two mo after the salvage surgery, he developed a second recurrence at right neck. Due to suboptimal performance status and his preference, he started erlotinib treatment. He achieved partial response after first 2 mo of erlotinib treatment, then complete response after total 6 mo of erlotinib treatment. He developed sever skin rash and diarrhea including Clostridium difficile infection during the course of erlotinib treatment requiring dose reduction and eventual discontinuation. He remained in complete remission for more than two years after discontinuation of erlotinib. CONCLUSION: We report a case of metastatic SCCHN achieving durable complete response from erlotinib. Patient experienced skin rash and diarrhea toxicities which were likely predictors of his treatment response.

The role of bile acids in cellular invasiveness of gastric cancer.

BACKGROUND: Bile acids have been implicated in the development of digestive tract malignancy by epidemiological, clinical and animal studies. The growth and transformation signaling by most of the bile acids is thought to be related to the induced cyclooxygenase-2 (COX-2) expression and increased production of prostaglandin E2 (PGE2). The highly hydrophobic bile acids such as chenodeoxycholic acid (CD) and deoxycholic acid can promote carcinogenesis and stimulate the invasion of colon cancer cells. On the contrary, ursodeoxycholic acid (UDCA), a less hydrophobic stereoisomer of CD, inhibits proliferation and induces apoptosis in colon cancer cells. We examined the effects of bile acid on human gastric cancer cells MKN-74. METHODS: Early-passage human gastric cancer MKN-74 cells were used for drug treatment, preparation of whole cell lysates, subcellular extracts and Western blot analysis. The levels of PGE2 released by the cells were measured by enzyme inummoassay to indicate COX-2 enzymatic activity. Cellular invasion assay was performed in Boyden chamber. RESULTS: Exposure of CD led to activation of protein kinase C (PKC) alpha, increased COX-2 expression and increased PGE2 synthesis. The induced COX-2 protein expression could be detected within 4 h exposure of 200 µM CD, and it was dose- and time-dependent. PGE2 is the product of COX-2, and has been reported to cause tumor invasion and angiogenesis in animal study. Safingol (SAF), a PKC inhibitor, suppressed the COX-2 protein expression and PGE2 production by CD in MKN-74. Furthermore, UDCA suppressed PGE2 production by CD but did not affect COX-2 protein expression induced by CD. Using a Boyden chamber invasion assay, both SAF and UDCA impeded CD induced tumor invasiveness of MKN-74 by 30-50%. CONCLUSIONS: Our results indicate that signaling of hydrophobic bile acid such as CD in gastric cancer cells is through PKC activation and COX-2 induction, which leads to increased cellular invasion. By perturbing the bile acid pool, UDCA attenuates CD-induced PGE2 synthesis and tumor invasiveness.

Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma.

Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma.

Critical appraisal of the role of sorafenib in the management of hepatocellular carcinoma.

Sorafenib is an oral multiple kinase inhibitor that blocks Raf, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor. It has been approved in the US and Europe for the treatment of advanced hepatocellular carcinoma (HCC). Sorafenib has demonstrated a 44% increase in survival for advanced HCC patients, compared with best supportive care alone. We have reviewed the pharmacology, pivotal studies, and safety data for this agent. Sorafenib is the first systemic drug demonstrating a significant survival benefit, and is the standard of care for patients with advanced HCC for whom no potential curative option is available.