The death of tech pioneer and Apple co-founder Steve Jobs on Wednesday has prompted mourning and gadget-clutching around the world. Although Jobs’ family did not disclose the cause of his death, speculations abound that a rare form of pancreatic cancer did him in. In 2004, Jobs was diagnosed with an islet cell neuroendocrine tumor, and underwent surgery (a pancreaticoduodenectomy, or “Whipple procedure”) to remove the tumor later that year. He declared himself cured — but in 2008, his frail appearance suggested that he was ill once more. Jobs had a liver transplant in 2009, went on medical leave in January 2011, and resigned from the company just a month and a half ago, on 24 August. He died yesterday. He was 56.
Most pancreatic cancers have a poor prognosis, but Jobs’ version was a curable type. The most successful treatment for neuroendocrine pancreatic cancer is chemotherapy, says Jonathan Strosberg, a neuroendocrine oncologist at the H. Lee Moffitt Cancer Center in Tampa, Florida, who has had particular luck treating patients with the drugs capecitabine and temozolomide. Both agents have around 70% response rates, and a clinical trial is underway to test these drugs in combination on neuroendocrine tumors.
But there’s been little formal study of these older agents. “Chemotherapy needs to be tested in larger randomized clinical trials,” says Strosberg, Unfortunately, “it’s been tough.” Many of these chemotherapies are “reaching end of their lives as non-generic medications,” he says, “so there’s not a lot of pharmaceutical support.”
Despite the small patient population, drugs are under development to treat the rare cancer. In May, the US Food and Drug Administration approved two new drugs for pancreatic neuroendocrine tumors: Novartis’s Afinitor (everolimus) and Pfizer’s Sutent (sunitinib), both of which extended people’s lives by 5–6 months on average in phase 3 trials.
Many other drugs are currently in phase 2 trials. The US National Cancer Institute is testing Roche’s Avastin (bevacizumab) in hand with Afinitor and Novartis’s Sandostatin (octreotide). Sandostatin mimics the protein somatostatin, which inhibits the secretion of a growth hormone and interacts with two specific receptors on the surface of most neuroendocrine tumors. Strosberg is also testing another somatostatin mimic, Novartis’ pasireotide, which interacts instead with four different receptors on the tumor cells. “We hope it’s a better drug than the current standard of care,” he says. In addition, Strosberg has initiated a phase 2 trial for Pfizer’s axitinib, which, like Avastin, inhibits new blood vessel growth and is particularly valuable in more vascular cancers, such as those of the pancreas and kidney. Other drugs under investigation are GlaxoSmithKline’s Votrient (pazopanib), currently approved for renal cell carcinoma, and Bayer’s kidney and liver cancer drug Nexavar (sorafenib). Plus, France’s Ministry of Health is on the hunt for biomarkers to predict the success of Sutent.
Jobs kept his medical care under wraps, so it’s not known what treatments he used. But Strosberg says that his liver transplant was probably a mistake. “The cancer almost always comes back after transplant, and the putative benefit of liver transplant is very hard to prove,” he says. “I hardly ever recommend liver transplants.”
Image: via Wikimedia Commons
