ONCOLOGY Vol 24 No 3

The US Food and Drug Administration recently approved rituximab (Rituxan) to treat certain patients with chronic lymphocytic leukemia (CLL).

The first issue deserving comment is the heterogeneity of stage III disease. Stage IIIA N2 non–small-cell lung cancer (NSCLC) includes patients with at least one “incidental” N2 node detected at the time of surgical resection in patients who had a negative mediastinal evaluation (including mediastinoscopy) preoperatively. It also includes patients whose initial computed tomography (CT) and positron-emission tomography (PET) scans show multiple bulky (> 2 cm) nodes that are confirmed by either mediastinoscopy or endobronchial ultrasound-guided bronchoscopy.

Dr. Bennett and colleagues have provided a thorough and balanced history of the rise and fall of erythropoietin-stimulating agents (ESAs) in cancer-associated anemia. Their review encourages us to think about the lessons learned from this history-lessons about medical progress, the importance of clinical research in guiding clinical practice, and the role of the US Food and Drug Administration (FDA) in protecting patients

The perception and reality of the clinical value of erythropoiesis-stimulating agents (ESAs) in cancer supportive care have undergone a dramatic transformation since their initial use in 1990. The perception of ESA value in patients has evolved from panacea to miscreant over a 2-decade period of laboratory research, clinical trial data, and postmarketing experience. Meanwhile, the real clinical benefits of ESAs have changed very little from those described in the joint American Society of Clinical Oncology/American Society of Hematology guidelines originally published in 2002.[1] Even then, the value of initiation of ESAs was clear only in patients with hemoglobin values < 10 g/dL; quality-of-life measures produced inconsistent and, therefore, clinically inapplicable, results; and ESA use was shown to reduce the proportion of patients requiring red blood cell (RBC) transfusions by approximately 20%. The reality of ESA use that came to light following approval was increased mortality rates in certain populations, higher tumor progression and cancer recurrence rates, and more frequent and severe serious adverse effects including thromboembolism, stroke, and cardiovascular events.

The patient is a 26-year-old woman with a complex oncologic history. At 1 year of age, she was diagnosed with a stage III abdominal neuroblastoma, which was treated, and again at age 9, she had a recurrence of neuroblastoma in the left axilla. She was in her usual state of good health until 18 months ago, when she presented with hematuria and was found to have a right-sided kidney mass.

The US Food and Drug Administration’s Office of Oncology Drug Products approved more than 50 new indications for the use of oncology and hematology drugs and biologics between July 2005, when the office began reviewing marketing applications, and the end of 2007, according to a new agency study.

Novartis recently announced that nilotinib (Tasigna) has been granted priority review by the US Food and Drug Administration (FDA) for the treatment of adult patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in chronic phase.

The combination of oxaliplatin plus fluorouracil/leucovorin is known as the FOLFOX regimen, and it has become a standard regimen for colorectal cancer (CRC), both as adjuvant therapy and as treatment for metastatic disease. Unfortunately, platinum-based chemotherapies also produce neurotoxicity as a side effect. Neurotoxicity is the most common dose-limiting toxicity of oxaliplatin, and it is one of the major causes for patients to stop receiving chemotherapy. It can manifest as either of two distinct syndromes: a transient, acute syndrome that can appear during or shortly after the infusion (~1%–2% of patients), and a dose-limiting, cumulative sensory neuropathy. Calcium/magnesium (Ca/Mg) infusions have been used to decrease the incidence of oxaliplatin-induced neuropathy. The actual utility of Ca/Mg infusions in this setting has been an interesting and controversial topic. They may reduce the severity of neurotoxicity, but some investigators have questioned whether they also will alter the efficacy of these chemotherapy regimens. In this paper, we review the clinical data concerning the usefulness of Ca/Mg infusions in reducing the incidence of oxaliplatin-induced neuropathy as well as their effect on responsiveness to chemotherapy.

Lycopene is a carotenoid found in tomatoes, grapefruit, watermelons, and papaya. It is also synthesized by plants and microorganisms, but cannot be synthesized by the human body and can only be obtained via diet. Lycopene as a dietary supplement is a potent antioxidant used to help prevent cancer, heart disease, and macular degeneration. It is classified as a nonprovitamin A carotenoid because it cannot be converted to vitamin A.

Probably no other topic in thoracic oncology has resulted in more controversy than that of the management of locally advanced non–small-cell lung cancer (NSCLC). Although recent large randomized studies have yielded more reliable and objective data on which to base treatment decisions than were available a decade ago, management of these patients is still influenced by specialty bias and philosophical beliefs.

Anemia is a widely prevalent complication among cancer patients. At the time of diagnosis, 30% to 40% of patients with non-Hodgkin lymphoma or Hodgkin lymphoma and up to 70% of patients with multiple myeloma are anemic; rates are higher among persons with myelodysplastic syndromes. Among patients with solid cancers or lymphomas, up to half develop anemia following chemotherapy. For almost 2 decades, erythropoiesis-stimulating agents (ESAs) were the primary treatment for cancer-related anemia. However, reassessments of benefits and risks of ESAs for cancer-associated anemia have occurred internationally. We reviewed guidelines and notifications from regulatory agencies and manufacturers, reimbursement policies, and utilization for ESAs in the cancer and chronic kidney disease settings within the United States, Europe, and Canada. In 2008 the US Food and Drug Administration (FDA) restricted ESAs from cancer patients seeking cure. Reimbursement is limited to hemoglobin levels < 10 g/dL. In the United States, ESA usage increased 340% between 2001 and 2006, and decreased 60% since 2007. The European Medicines Agency (EMEA) recommended that ESA benefits do not outweigh risks. In Europe between 2001 and 2006, ESA use increased 51%; since 2006, use decreased by 10%. In 2009, Canadian manufacturers recommended usage based on patient preferences. In Canada in 2007, approximately 20% of anemic cancer patients received ESAs, a 20% increase since 2004. In contrast to Europe, where ESA use has increased over time, reassessments of ESA-associated safety concerns in the United States have resulted in marked decrements in ESA use among cancer patients.

Despite recent therapeutic advances, lung cancer continues to be one of the leading causes of cancer-related mortality. Of the various histologic subtypes, non–small-cell lung cancer (NSCLC) is the most common-accounting for approximately 85% of all lung cancers-and will be the focus of this article. In general, the treatment of lung cancer may include surgery, radiation therapy, systemic therapy (eg, chemotherapy with or without targeted therapy), or a combination of the above. Surgery continues to offer the best chance of long-term cure. The initial treatment of stage I and II NSCLC usually entails surgical resection, whereas stage IV disease is primarily treated with systemic agents, in light of the lack of curative potential with surgery and/or radiation therapy alone. It is locally advanced NSCLC, including stage IIIA and IIIB disease, that continues to pose a therapeutic dilemma, given its heterogeneous nature.

Hematologists/oncologists and other physicians can expect to encounter an increasing number of patients with multiple myeloma in the coming years. Between 1997 and 2006, the incidence rate of myeloma declined in the United States, but the burden (the number of incident cases) increased.[1]