Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma.

CONTEXT: Combination chemotherapy with FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) was shown to be effective in a large phase III trial. OBJECTIVE: The purpose of this study was to examine the tolerance and effectiveness of FOLFIRINOX as practiced outside of the confines of a clinical trial and to document any dose modifications used by practicing oncologists. METHODS: Data on patients with all stages of pancreatic adenocarcinoma treated with FOLFIRINOX at three institutions was analyzed for efficacy, tolerance, and use of any dose modifications. RESULTS: Total of 61 patients was included in this review. Median age was 58 years (range: 37 to 72 years), 33 were male (54.1%) and majority had ECOG performance of 0 or 1 (86.9%, 53 patients). Thirty-eight (62.3%) had metastatic disease, while 23 (37.7%) were treated for locally advanced or borderline resectable disease. Patients were treated with a median number of four cycles of FOLFIRINOX, with dose modifications in 58.3% (176/302) of all cycles. Ten patients had stable disease (16.4%), four had a partial response (6.6%) while eight had progressive disease (13.1%) on best imaging following therapy. Median progression-free survival and overall survival were 7.5 months and 13.5 months, respectively. The most common grade 3-4 adverse event was neutropenia at 19.7% (12 cases), with 4.9% (3 cases) rate of febrile neutropenia. Twenty-one patients (34.4%) were hospitalized as a result of therapy but there were no therapy-related deaths. Twenty-three (37.7%) had therapy eventually discontinued as a result of adverse events. CONCLUSION: Despite substantial rates of adverse events and use of dose modifications, FOLFIRINOX was found to be clinically effective in both metastatic and non-metastatic patients. Regimen toxicity did not detract from overall response and survival.

Papillary Renal Carcinoma Presenting as a Cancer of Unknown Primary (CUP) and Diagnosed through Gene Expression Profiling.

Cancer of unknown primary (CUP) is a clinical syndrome representing many types of cancers and diagnoses are typically made after review of clinical presentation, pathology (including immunohistochemical staining) and imaging studies. Treatment with systemic chemotherapy has been shown to result in fairly reproducible objective response rates. Herein, a case of a patient who was initially diagnosed with a poorly differentiated adenocarcinoma of unknown origin is reported. After mRNA gene expression profiling (commercially available CancerTYPE ID), a specific diagnosis of papillary renal cell carcinoma (RCC) was made and then confirmed with additional immunohistochemical staining. The patient was treated with targeted therapy and an objective radiographic response was seen. A literature review suggests this to be the first patient with papillary RCC, identified by molecular profiling, and benefitting from a targeted agent that otherwise would not have been considered in the setting of CUP. This case underscores the importance of considering the use of newer testing technologies in the interest of offering patients more specific, targeted therapy in order to improve efficacy and spare patients toxicities of less specific, empiric chemotherapeutic regimens.

You can't judge a book by its cover or a tumor by its expression profile.

Expression profiling has shown great promise in matching cancers of unknown primary to likely primary tumors of origin based on patterns of mRNA expression. However, it remains uncertain as to whether even well matched tumors will demonstrate the clinical features, such as rate of progression, of their matched counterparts. In this case report, we note that based on histology, immunohistochemistry and expression profile this patient's poorly differentiated neuroendocrine tumor would have been expected to grow very rapidly on no therapy. Instead, this cancer was very indolent, with only very little radiographic progression over several years. We believe this report represents a remarkable case of a tumor where features, including expression profile, would not at all have accurately predicted the clinical course seen. While some series have suggested that matching by expression profiling predicts outcome, this case shows a dramatically different result.

Marked response to single agent trastuzumab in a patient with metastatic HER-2 gene amplified rectal cancer.

Overexpression or HER-2 gene amplification occurs in approximately 25% of invasive breast cancers and predicts response to the targeting therapeutic antibody trastuzumab (1). In this report, trastuzumab was used in the treatment of a patient with metastatic colorectal cancer harboring HER-2 gene amplification and overexpression. There was a marked radiographic response to the trastuzumab. If a larger series confirms the efficacy of trastuzumab use in patients with colorectal cancers with HER-2 gene amplification, trastuzumab could help improve the outlook for patients with this unusual colorectal cancer variant.

Evolutionary maintenance of oncogenesis.

BACKGROUND: Transformation of normal cells into cells with malignant phenotypes is often the result of loss of tumor suppressor gene (TSG) function after exposure to a carcinogen. CONCLUSIONS: We propose that TSGs susceptible to mutation and consequent loss of function are evolutionarily preserved in normal cell genomes so that the cells survive mutation-inducing insults and thereby evade apoptosis. While the mutations produced in TSGs confer cellular persistence and preclude apoptosis, oncogenesis is the untoward consequence. Proto-oncogenes might similarly be maintained and contain evolutionarily selected and fixed sequences susceptible to mutations (oncogene activation) that prevent cell death but ironically result in host death from malignancy.

Biological therapy update in colorectal cancer.

Colon and rectal cancer remain the second most common cause of cancer death in the US. Advances in the past 10 years have resulted in improved outcomes for patients. In addition to newer chemotherapeutics agents, the so-called 'targeted' or 'biological' therapies have improved survival in patients with metastatic disease. This review aims to summarize the mechanistic basis for the usefulness of these agents, the key clinical trials demonstrating their efficacy, and the studies now initiated with the hope of further incorporating their use in treating colon and rectal cancer.