Assistant Professor, Department of Gastrointestinal Medical Oncology
This past weekend, experts in gastrointestinal malignancies gathered to review interval advances in the field at the ASCO Gastrointestinal Cancer Symposium. Of the studies presented, three are worth noting that are likely to change the standard therapies or provide exciting research opportunities.
Neuroendocrine Tumors
Treatment for neuroendocrine tumors has made recent advances, exemplified by a study reported at the meeting for the oral tyrosine kinase inhibitor sunitinib. Pancreatic neuroendocrine tumor (PNET) is one of the most common subtypes of an uncommon tumor. PNETs traditionally have been treated variably with somatostatin analogs, interferon or cytotoxic chemotherapy, although several recent studies have demonstrated promising molecularly targeted treatment approaches.
This past weekend, experts in gastrointestinal malignancies gathered to review interval advances in the field at the ASCO Gastrointestinal Cancer Symposium. Of the studies presented, three are worth noting that are likely to change the standard therapies or provide exciting research opportunities.Neuroendocrine Tumors
Treatment for neuroendocrine tumors has made recent advances, exemplified by a study reported at the meeting for the oral tyrosine kinase inhibitor sunitinib. Pancreatic neuroendocrine tumor (PNET) is one of the most common subtypes of an uncommon tumor. PNETs traditionally have been treated variably with somatostatin analogs, interferon or cytotoxic chemotherapy, although several recent studies have demonstrated promising molecularly targeted treatment approaches.
Laboratory studies have suggested that treatment with agents that inhibit blood vessel formation may provide benefit. Sunitinib is an inhibitor of vascular endothelial growth factor signaling, one of the main drivers of new blood vessel growth.
In an international randomized Phase III study, 340 patients with advanced PNET were planned to be enrolled in a study comparing observation alone to a daily oral dose of sunitinib. After only 171 were enrolled, the study was stopped as it was already evident that patients treated with sunitinib had improvements in their cancer and were living longer.
On average, patients had their disease controlled for 11.4 months with sunitinib treatment, compared to an average time to tumor growth of 5.5 months with no therapy. Similarly, sunitinib-treated patients lived twice as long. Side effects from the treatment were modest, and included development of high blood pressure and irritation/redness of the palms and soles. If validated, these results will open a new treatment option for patients with advanced pancreatic neuroendocrine tumors.
Pancreatic Cancer
Traditional pancreatic cancers have been difficult to treat and very few advances have been made in the field over the past few years. Recent data has suggested that the insulin-like growth factor receptor (IGFR) pathway may be a promising candidate for treatment of many cancers, including pancreatic cancer based on limited laboratory studies.
Pancreatic Cancer
Traditional pancreatic cancers have been difficult to treat and very few advances have been made in the field over the past few years. Recent data has suggested that the insulin-like growth factor receptor (IGFR) pathway may be a promising candidate for treatment of many cancers, including pancreatic cancer based on limited laboratory studies.
One of the first and largest studies to evaluate an inhibitor of IGFR in combination with chemotherapy was recently completed at M. D. Anderson and reported by Milind Javle, M.D., in an oral session. In this study, patients were treated with a monoclonal antibody to IGFR in combination with chemotherapy. The study demonstrated that the combination was safe, with some patients having prolonged disease control. A Phase II portion of the study is ongoing using a novel adaptive study design, which allocates more patients to the treatment arm that appears to be performing the best.
Importantly, Dr. Javle and his colleagues are concurrently collecting important information to understand how the tumor is responding on a molecular level to the novel therapies. This combination of concurrent molecular studies and novel study design was praised by the expert discussant at the meeting as an optimal model for future studies in pancreatic cancer.
Colon Cancer
Significant effort has been focused on new techniques to detect and prevent colon cancer. One recent advance was presented by K.P. Raj, M.D., on the role of polyamines in colon cancer development.
Importantly, Dr. Javle and his colleagues are concurrently collecting important information to understand how the tumor is responding on a molecular level to the novel therapies. This combination of concurrent molecular studies and novel study design was praised by the expert discussant at the meeting as an optimal model for future studies in pancreatic cancer.
Colon Cancer
Significant effort has been focused on new techniques to detect and prevent colon cancer. One recent advance was presented by K.P. Raj, M.D., on the role of polyamines in colon cancer development.
Previously animal studies suggest that very high levels of diet intake of polyamines can increase colon cancer, while decreasing polyamines can reduce colon cancer development. Polyamines come from two sources: they are synthesized in the body as well as ingested in the normal diet, with highest levels in orange juice, red meat, peas, corn and nuts, among others.
A large chemoprevention study of DFMO and sulindac had previously shown a 70% reduction in new precancerous lesions. In this study, 375 patients with prior precancerous lesions were randomized to DFMO/sulindac or placebo, with all patients obtaining normal screening colonoscopies. DFMO and sulindac inhibit new synthesis of polyamines in the body, among other potential mechanisms of actions. Dr. Raj analyzed the dietary intake of polyamines in patients on this study to determine the role for the dietary forms of polyamine in cancer formation.
These results demonstrated that patients who reported high dietary intake of polyamines had larger and more advanced colon polyps prior to starting the study. For patients with lower reported dietary intake of polyamine, treatment with DFMO and sulindac resulted in a 94% reduction in advanced cancers. In contrast, in patients with high dietary intake of polyamines, there was no benefit seen with the chemoprevention. Further studies are needed to understand this finding, but it suggests that in high-risk patients, chemoprevention may only be beneficial with appropriate dietary modifications.
Collectively, these findings reiterate the active ongoing research in gastrointestinal malignancies, while highlighting areas where significant improvements are needed in our ability to detect, diagnosis and treat gastrointestinal cancers.
A large chemoprevention study of DFMO and sulindac had previously shown a 70% reduction in new precancerous lesions. In this study, 375 patients with prior precancerous lesions were randomized to DFMO/sulindac or placebo, with all patients obtaining normal screening colonoscopies. DFMO and sulindac inhibit new synthesis of polyamines in the body, among other potential mechanisms of actions. Dr. Raj analyzed the dietary intake of polyamines in patients on this study to determine the role for the dietary forms of polyamine in cancer formation.
These results demonstrated that patients who reported high dietary intake of polyamines had larger and more advanced colon polyps prior to starting the study. For patients with lower reported dietary intake of polyamine, treatment with DFMO and sulindac resulted in a 94% reduction in advanced cancers. In contrast, in patients with high dietary intake of polyamines, there was no benefit seen with the chemoprevention. Further studies are needed to understand this finding, but it suggests that in high-risk patients, chemoprevention may only be beneficial with appropriate dietary modifications.
Collectively, these findings reiterate the active ongoing research in gastrointestinal malignancies, while highlighting areas where significant improvements are needed in our ability to detect, diagnosis and treat gastrointestinal cancers.
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