New Drugs Bring Hope for Combating Cancer

Statistics from the American Cancer Society show that an estimated 1,444,920 new cases of cancer are expected in 2007, along with 559,650 cancer deaths.1 Each time a new oncology drug is approved, hope emerges for the millions of individuals diagnosed with cancer. In 2007, the FDA approved lapatinib. In 2006, the agency had approved vorinostat, panitumumab, dasatinib, and sunitinib for the treatment of specific types of cancers. This article will review these new agents (from the latest to the earliest; Table2-7).Lapatinib

In March 2007, the FDA approved lapatinib (Tykerb), a new molecular entity that is classified as a kinase inhibitor. Lapatinib is indicated for use, in combination with the agent capecitabine, in treating patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received previous therapy including an anthracycline, a taxane, and trastuzumab.2Lapatinib should be used with caution in individuals with preexisting cardiac conditions, including uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure. In addition, lapatinib has been associated with incidences of decreases in left ventricular ejection fraction (LVEF). LVEF should be monitored in all patients before and during treatment with lapatinib.2 Doses should be reduced in individuals with severe hepatic impairment, and this agent should not be used in pregnant women.^{2 Lapatinib has been shown to interact with drugs that are metabolized by CYP3A4 or CYP2C8.}2This drug is available in 250-mg tablets. A daily dose of 1250 mg (5 tablets) should be taken for 21 days and in combination with capecitabine on days 1 to 14 of a 21-day cycle. Lapatinib should be administered at least 1 hour before or after a meal.Vorinostat

In October 2006, the FDA approved vorinostat (Zolinza) as part of its Orphan Drug Program.^{3 Vorinostat is a histone deacetylase (HDAC) inhibitor. It is indicated for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent, or recurrent disease on or following 2 systemic therapies.}4The recommended dose is 400 mg daily with food. Patients should be counseled on the importance of adequate fluid intake (at least 2 L/day of fluid) to prevent dehydration. They should promptly report excessive vomiting or diarrhea to their physician. Monitoring of complete blood count (CBC) and electrolytes such as potassium, magnesium, and calcium should be performed every 2 weeks during the first 2 months of therapy and then monthly thereafter.4The most serious adverse reactions reported were pulmonary embolism and anemia. Researchers have found that the use of vorinostat and coumarinderivative anticoagulants concomitantly may prolong the prothrombin time (PT) and the international normalized ratio (INR) in patients. Therefore, it is important for patients concurrently taking vorinostat and a coumarin derivative to have their PT and INR values monitored regularly.^{4 In addition, because there is a risk of severe thrombocytopenia and gastrointestinal (GI) bleeding associated with the concomitant use of vorinostat and other HDAC inhibitors, such as valproic acid, individuals should have their platelets monitored every 2 weeks.}4 This agent should not be used by pregnant women or those planning to become pregnant.Panitumumab

Panitumumab (Vectibix) is a recombinant human IgG2 kappa monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). It is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma with progression of disease on or following treatment with fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy regimens.^{5 Studies conducted on panitumumab report no formal drug?drug interactions.}5The recommended dose of panitumumab is 6 mg/kg administered via intravenous infusion over 60 minutes every 14 days. Doses >1000 mg should be infused over 90 minutes. If an individual experiences mild-to-moderate infusion reactions, reducing the infusion rate by 50% is recommended. If an individual experiences severe infusion reactions, the infusion should be discontinued immediately.5Patients receiving panitumumab should be monitored at regular intervals for hypomagnesemia and also for hypocalcemia during and for 8 weeks after completion of therapy with panitumumab. Studies on panitumumab report that its use may impair fertility in women, as well as causing prolonged menstrual cycles and/or amenorrhea.5References

• Cancer Deaths Down for the Second Year. Available at American Cancer Society Web site at: www.cancer.org/docroot/NWS/content/NWS_1_1x_Cancer_Deaths_Down_Again.asp.
• Tykerb Prescribing Information. Available at: www.tykerb.com.
• FDA Approves New Drug for Skin Cancer. Available at: www.fda.gov/bbs/topics/NEWS/2006/NEW01484.html.
• Zolinza Prescribing Information. Available at: www.zolinza.com.
• Vectibix Prescribing Information. Available at: www.vectibix.com.
• Sprycel Prescribing Information. Available at: www.sprycel.com.
• Sunitinib Prescribing Information. Available at: www.sunitinib.com.