Pancreatic Neuroendocrine Tumors: A Lesser Threat than Adenocarcinomas, but Still Hard to Treat


Pancreatic neuroendocrine tumors (PNETs) constitute only about 3% to 5% of all pancreatic cancers. Compared to the most common pancreatic cancer—adenocarcinoma (aka exocrine tumors), PNETs have a longer disease course and better prognosis; the 5-year survival rate is 42% for PNETs, but only about 5% to 6% for adenocarcinomas. When PNETs are localized, they can usually be removed by surgery. However, PNETs tend to metastasize, most often to the liver, and present a formidable treatment challenge at this stage. Continue reading…


Lung NETs and Their Treatment


Cancers that arise in the lung are mostly of the type known as NSCLC (non-small cell lung carcinoma). A much smaller proportion of lung tumors arise from neuroendocrine cells in the lungs. These cells (which are also found in most other organs) secrete a variety of hormones that are necessary for normal organ function, as well as for healing after injury or infection. Like other lung cells, neuroendocrine cells may transform to become cancers. Lung cancers that arise from neuroendocrine cells are called pulmonary neuroendocrine tumors (NETs), or lung NETs. Continue reading…


Maintenance Sunitinib Improved PFS in Extensive-Stage SCLC

“The use of maintenance sunitinib improved progression-free survival (PFS) over placebo among patients with untreated extensive-stage small-cell lung cancer (SCLC) in a new phase II study.

“ ‘Most of the 30,000 patients newly diagnosed each year with SCLC in the United States have extensive-stage disease,’ wrote study authors led by Neal E. Ready, MD, PhD, of Duke University Medical Center in Durham, North Carolina. ‘Despite achieving good disease control initially, patients with SCLC usually experience relapse within 6 months of first-line chemotherapy and often do not respond to subsequent chemotherapy.’

“In previous studies, maintenance chemotherapy after standard platinum-based therapy did not show any overall survival benefit. The new study aimed to test whether sunitinib, a small-molecule tyrosine kinase inhibitor that inhibits VEGF receptors and other targets. Results of the new study were published online ahead of print in the Journal of Clinical Oncology.

“The study enrolled a total of 144 patients, 49 of whom progressed or did not complete induction chemotherapy; 95 patients were randomly assigned to a placebo maintenance therapy group (46 patients) or a sunitinib maintenance therapy group (49 patients), and five patients on each arm did not receive the maintenance therapy. Sunitinib patients received 37.5 mg per day until progression.”


Lpath Reports Interim Data From Phase 2a Study for Anti-Cancer Drug, ASONEP

Editor’s note: Researchers are conducting a clinical trial with volunteer patients to test a new kidney cancer treatment called ASONEP. Specifically, the trial is testing the effectiveness of ASONEP for people with metastatic renal cell carcinoma (RCC) who were previously but unsuccessfully treated with at least one “VEGF inhibitor” drug (like Sutent, aka sunitinib) and no more than one “mTOR inhibitor” drug (like Afinitor, aka everolimus), with a maximum of three unsuccessful previous treatments overall. The clinical trial is ongoing, but interim results show that ASONEP is safe and hasn’t caused serious side effects. The researchers also said the drug appeared to show promise as a cancer-fighting treatment.

“Lpath, Inc. (NASDAQ: LPTN), the industry leader in bioactive lipid-targeted therapeutics, reported interim results in a Phase 2a single-arm, open-label trial where ASONEP™ is being investigated as a treatment for metastatic renal cell carcinoma (RCC) in patients that have failed at least one therapy involving a VEGF inhibitor (e.g., Sutent®/ sunitinib maleate) and no more than one mTOR inhibitor (e.g., Afinitor®/everolimus), with a maximum of three failed treatments in all. This patient population is considered “last line,” and the literature suggests cancer progression in this population within a one-to-two month time frame.

“Lpath has enrolled 26 patients in the study. ASONEP has a favorable safety profile thus far, with no serious adverse events (SAEs) deemed to be drug-related.

“The first 17 patients were initiated at a dose of 15 mg/kg. Of these “lower-dose” patients:  7 had progressive disease at or before the end of four months; 8 were progression-free at the four-month mark (with 1 of these patients deemed a partial responder per Response Evaluation Criteria in Solid Tumors (RECIST) criteria and with 3 of these patients experiencing reduced tumor volume, but not enough to be categorized as a RECIST-based partial responder); and 2 exited the study due to SAEs unrelated to the drug prior to the four-month mark (and are not considered evaluable). Notably, of the 8 patients that were stable or better as of month four, 2 are now in their fifteenth month on the study, 1 is in month thirteen, and 1 is in month ten. An additional patient was stable through month seven, but then missed six treatments during a vacation, and shortly thereafter progressed.”


Drugs to Avoid in Patients on Tyrosine Kinase Inhibitors

Editor’s note: More and more people with cancer are being treated with drugs known as tyrosine kinase inhibitors (TKIs). As with any other drug, oncologists who prescribe TKIs must be aware of other drugs a patient is taking to ensure there will not be a dangerous drug-drug interaction. Researchers recently published a report outlining known and potential drug-drug interactions between TKIs and other drugs. Oncologists and patients may wish to take these into account when considering cancer treatment with TKIs.

“With the rapid and widespread uptake of tyrosine kinase inhibitors (TKIs) in oncology over the past several years, serious drug–drug interactions are an “increasing risk,” according a new report.

“To guarantee the safe use of TKIs, ‘a drugs review for each patient is needed,’ write Frank G.A. Jansman, PharmD, PhD, from Deventer Hospital in the Netherlands, and colleagues in a review published in the July issue of the Lancet Oncology.

“The review provides a comprehensive overview of known and suspected interactions between TKIs and conventional prescribed drugs, over-the-counter drugs, and herbal medicines.

“All 15 TKIs approved to date by the US Food and Drug Administration or the European Medicines Agency are evaluated.

“They are axitinib (Inlyta, Pfizer), crizotinib (Xalkori, Pfizer), dasatinib (Sprycel, Bristol-Myers Squibb and Otsuka America), erlotinib (Tarceva, Osi Pharmaceuticals), gefitinib (Iressa, AstraZeneca), imatinib (Gleevec, Novartis), lapatinib (Tykerb, GlaxoSmithKline), nilotinib (Tasigna, Novartis), pazopanib (Votrient, GlaxoSmithKline), regorafenib (Stivarga, Bayer), ruxolitinib (Jakafi, Incyte), sorafenib (Nexavar, Bayer), sunitinib (Sutent, Pfizer), vandetanib (Caprelsa, AstraZeneca), and vemurafenib (Zelboraf, Roche).”


Sunitinib or Everolimus First-Line for Kidney Cancer?

Editor’s note: Researchers conducted a clinical trial with volunteer patients to compare two drugs for kidney cancer: everolimus (aka Afinitor) and sunitinib (aka Sutent). The results showed that sunitinib is more effective as a first-line treatment for people diagnosed with metastatic renal cell carcinoma (mRCC). The standard treatment already widely prescribed to mRCC patients is sunitinib or a similar drug, followed by everolimus if the disease worsens. Oncologists wondered if everolimus could be a first-line therapy for mRCC, but it appears that the current standard is the better choice.

“Everolimus (Afinitor, Novartis) is not as effective as sunitinib (Sutent, Pfizer) in the first-line setting for patients with metastatic renal cell carcinoma, and it has a different toxicity profile, according to a phase 2 randomized direct comparator trial.

“The study, known as RECORD-3, was published online July 21 in the Journal of Clinical Oncology.

” ‘The hope was that everolimus would be better tolerated and as good as sunitinib in first-line treatment,’ said lead investigator Robert Motzer, MD, attending physician in the genitourinary oncology service at the Memorial Sloan Kettering Cancer Center and professor of medicine at Weill Medical College at Cornell University in New York City.

“However, ‘in first-line therapy, the efficacy of sunitinib appeared to be better than everolimus. It is clear that sunitinib remains the standard first-line therapy,’ he explained.

” ‘The current paradigm of sunitinib followed by everolimus at progression should be maintained. The experimental sequence of everolimus first followed by sunitinib second did not appear to be as effective,’ Dr. Motzer reported.”


Alternative Sunitinib Treatment Schedules for mRCC May be Worth the Switch

“Some patients with metastatic renal cell carcinoma (mRCC) who are switched from a traditional sunitinib treatment schedule to an alternative schedule fare better on survival measures and suffer fewer adverse events, a Japanese study has found.

“The switch from traditional to alternative schedules was recently found to be effective. But, ‘Japanese patients with mRCC experience substantially different [adverse events] than do patients in many other nations, presumably because of underlying genetic differences’, the authors write.

“They retrospectively reviewed the medical records of 54 patients with mRCC who received sunitinib treatment as first-line therapy between May 2006 and June 2012.”


18F-FGD-PET Measures Predict mRCC TKI Response

“Positron emission tomography (PET) could be used to predict the response of metastatic renal cell carcinoma (mRCC) to tyrosine kinase inhibitor (TKI) therapy within a couple of weeks of a patient beginning treatment, research suggests.

“Changes in volume-based metabolic parameters of 18F-fluorodeoxyglucose (FDG) before and after 14 days of treatment with sunitinib, sorafenib or pazopanib significantly correlated with progression-free and overall survival, say Jacob Farnebo (Karokinska University Hospital, Stockholm, Sweden) and co-authors.”

Editor’s note: Doctors and patients can make more informed treatment decisions if they can more closely monitor how well a treatment is working and predict how well it is likely to work in the long run. This story discusses how monitoring with positron emission tomography (PET) within the first couple of weeks of treatment might help predict how well certain drugs will work. PET scanning produces 3-D images of the inside of the body. Scientists conducted a study in which they gave PET scans to volunteer patients who were being treated with the drugs sunitinib, sorafenib, or pazopanib for metastatic renal cell carcinoma (mRCC). They found that, within two weeks of the patients starting treatment, they could use information from the PET scans to determine the effectiveness of the treatment. They were able to link these PET scan results to how long the patients lived and how much time passed before patients’ disease worsened.


ASCO: Sunitinib Improves PFS in Small-Cell Lung Cancer

A randomized, phase II trial showed improved progression-free survival in small-cell lung cancer with maintenance sunitinib vs placebo following standard chemotherapy, according to results presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.