Although gemcitabine is approved for use as a single agent in metastatic pancreatic cancer, the overall response rate is low at less than 10%, with complete responses being exceedingly rare. Intense efforts have focused on incorporating gemcitabine into various combination regimens, and currently, the most commonly used regimen for the first-line treatment of metastatic pancreatic cancer is gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel [Abraxane]). In patients who are able to tolerate a more aggressive approach, the FOLFIRINOX regimen, which includes intravenous 5-FU, irinotecan, and oxaliplatin, has become a widely used therapy. Single-agent irinotecan or liposomal irinotecan in combination with intravenous 5-FU are appropriate treatment options in the second-line setting. In patients with early-stage pancreatic cancer who have undergone successful surgical resection, adjuvant chemotherapy with either single-agent gemcitabine or 5-FU/leucovorin is recommended.
Hepatocellular cancer (HCC) has been a relatively difficult tumor to treat as it frequently occurs in the context of chronic liver disease and cirrhosis. It is usually diagnosed late in the course of chronic liver disease, and a large majority of patients have underlying poor liver function and only limited hepatic reserve. In general, HCC is considered to be a chemotherapy-resistant disease, and palliative chemotherapy is usually not recommended as first-line therapy in patients with unresectable or advanced HCC. Single-agent sorafenib therapy is currently approved for advanced or unresectable HCC, and in patients who have progressed on front-line sorafenib therapy, the small molecule tyrosine kinase inhibitor regorafenib is recommended.
Lung cancer is divided into two main histopathologic subtypes, non-small cell and small cell. Non-small cell lung cancer (NSCLC) makes up about 75–80% of all cases of lung cancer, and this group includes adenocarcinoma, squamous cell cancer, and large cell cancer, while small cell lung cancer (SCLC) makes up the remaining 20–25%. When NSCLC is diagnosed in an advanced stage with metastatic disease, the prognosis is extremely poor, with a median survival of about 8 months. It is clear that prevention (primarily through avoidance of cigarette smoking) and early detection remain the most important means of control. When diagnosed at an early stage, surgical resection results in patient cure. Moreover, recent studies have shown that adjuvant platinum-based chemotherapy provides a survival benefit in patients with pathologic stage IB, II, and IIIA disease. However, in most cases, distant metastases have occurred at the time of diagnosis. In certain instances, radiation therapy can be offered for palliation of pain, airway obstruction, or bleeding and to treat patients whose performance status would not allow for more aggressive treatments.
In patients with advanced disease, systemic chemotherapy is generally recommended. Combination regimens that include a platinum agent (“platinum doublets”) appear superior to non-platinum doublets, and either cisplatin or carboplatin are appropriate platinum agents for such regimens. For the second drug, paclitaxel and vinorelbine appear to have activity independent of histology, while the antifolate pemetrexed should be used for non-squamous cell cancer, and gemcitabine for squamous cell cancer. For patients with good performance status and those with non-squamous histology, the combination of the anti-VEGF antibody bevacizumab with carboplatin and paclitaxel is a standard treatment option. In patients deemed not to be appropriate candidates for bevacizumab therapy and those with squamous cell histology, a platinum-based chemotherapy regimen in combination with the anti-EGFR antibody cetuximab is a reasonable treatment strategy. Maintenance chemotherapy with pemetrexed is now used in patients with non-squamous NSCLC whose disease has remained stable after four cycles of platinum-based first-line chemotherapy.