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Pancreatic Neoplasms: HELP
Articles by Ramya Thota
Based on 3 articles published since 2009
(Why 3 articles?)

Between 2009 and 2019, Ramya Thota wrote the following 3 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Review Preclinical Rationale for the Phase III Trials in Metastatic Pancreatic Cancer: Is Wishful Thinking Clouding Successful Drug Development for Pancreatic Cancer? 2017

Thota, Ramya / Maitra, Anirban / Berlin, Jordan D. ·From the *Division of Hematology/Oncology, Vanderbilt University, Nashville, TN; and †Sheikh Ahmed Pancreatic Cancer Research Center, Departments of Pathology and Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX. ·Pancreas · Pubmed #28085753.

ABSTRACT: Prior phase III trials in advanced pancreatic cancer have been predominantly unsuccessful. In this review, we attempt to understand how past preclinical data were translated into phase III clinical trials in metastatic pancreatic cancer as described in the article. A systematic literature review conducted through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases, from January 1997 to June 2015 using key words-phase III clinical trials, metastatic/advanced pancreatic adenocarcinoma or pancreatic cancer identified 30 randomized controlled trials (RCTs) that met criteria. The trials were limited to RCTs in the first-line treatment of patients with metastatic pancreatic cancer. The success rate of first-line phase III studies in advanced pancreatic cancer was only 13%. In 60% of the RCTs, no preclinical experiments were referenced in biologically cognate pancreatic models. Nine (30%) of the RCTs were designed based on preclinical evidence from in vitro cell lines alone without additional in vivo validation in xenograft models. It remains uncertain how strongly the preclinical data influence the development of clinical regimens but so far the studies developed based on more solid preclinical evidence have been successful.

2 Review Treatment of metastatic pancreatic adenocarcinoma: a review. 2014

Thota, Ramya / Pauff, James M / Berlin, Jordan D. · ·Oncology (Williston Park) · Pubmed #24683721.

ABSTRACT: Gemcitabine monotherapy has been the standard of care for patients with metastatic pancreatic cancer for several decades. Despite recent advances in various chemotherapeutic regimens and in the development of targeted therapies, metastatic pancreatic cancer remains highly resistant to chemotherapy. Previous studies of several combination regimens showed minimal or no significant change in overall survival compared with gemcitabine alone. Secreted protein acidic and rich in cysteine (SPARC) overexpression in pancreatic stromal fibroblasts is considered one of the major causes of chemotherapy resistance. The nanoparticle albumin-bound formulation of paclitaxel (nab-paclitaxel) has been found to be superior to other formulations of paclitaxel because of its favorable pharmacokinetic properties. Initial preclinical studies showed its synergistic effect with gemcitabine in pancreatic cancer, in which nab-paclitaxel is sequestered by SPARC to cause stromal depletion and increasing microvasculature, resulting in higher gemcitabine concentration within the tumor. In the recent phase III multinational Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), the combination of gemcitabine and nab-paclitaxel was shown to be superior to gemcitabine monotherapy, with an increase in median survival of 1.8 months. Combination therapy with gemcitabine plus erlotinib, or with gemcitabine plus nab-paclitaxel, or the multidrug regimen of leucovorin, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) can be considered as first-line chemotherapy for patients with metastatic pancreatic cancer. In this review we will discuss details of the recently approved combination of gemcitabine and nab-paclitaxel for first-line treatment of metastatic pancreatic adenocarcinoma and compare it with other therapeutic options.

3 Clinical Trial A Phase II Study of Ganetespib as Second-line or Third-line Therapy for Metastatic Pancreatic Cancer. 2018

Cardin, Dana B / Thota, Ramya / Goff, Laura W / Berlin, Jordan D / Jones, Clyde M / Ayers, Gregory D / Whisenant, Jennifer G / Chan, Emily. ·Department of Medicine. · Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center. · The Jones Clinic, Germantown, TN. · Department of Cancer Biostatistics, Vanderbilt University Medical Center, Nashville. ·Am J Clin Oncol · Pubmed #28301350.

ABSTRACT: OBJECTIVES: Heat shock protein 90 regulates multiple signaling proteins involved in key pathways of pancreatic cancer pathogenesis. Ganetespib binds to heat shock protein 90 and interferes with its binding to client proteins thus leading to inactivation and degradation of the signaling proteins that promote cancer progression. This phase II study was designed to evaluate the efficacy of ganetespib in patients with refractory metastatic pancreatic cancer (rMPC). METHODS: Patients with rMPC received 175 mg/m ganetespib intravenously once weekly for 3 weeks in 4-week cycles. Primary endpoint was disease control rate at 8 weeks, with a goal of 70%. Secondary endpoints were progression-free survival, overall survival, and safety. Simon's 2-stage design was used to assess futility and efficacy. Ganetespib was considered inactive if ≤8 patients among the first 15 treated had disease control after 8 weeks of treatment. RESULTS: Fourteen patients were treated on study. Grade 3 treatment-related toxicities were diarrhea, abdominal pain, fatigue, nausea, vomiting, and hyponatremia. Disease control rate at 8 weeks was 28.6%, and median progression-free survival and overall survival were 1.58 months and 4.57 months, respectively. Early stopping rules for lack of clinical efficacy led to study closure. CONCLUSIONS: Single-agent ganetespib was tolerable with only modest disease control in rMPC. This disease is resistant to chemotherapy, and given the emerging data in lung and rectal cancers, as well as in pancreatic cancer cell lines, suggesting improved activity of ganetespib in combination with cytotoxic agents, studies combining this agent with chemotherapy in rMPC are more likely to yield success.