Jeffrey Crawford, MD

For years, chemotherapy-associated myelosuppression has represented a major limitation to a patient’s tolerance of anticancer therapy. In addition, the clinical consequences of chemotherapy-induced myelosuppression (such as febrile neutropenia, dose reductions, or lengthy dose delays) may have had significant negative effects on quality of life or even response to treatment.

For years, chemotherapy-associated myelosuppression has represented a major limitation to a patient's tolerance of anticancer therapy. In addition, the clinical consequences of chemotherapy-induced myelosuppression (such as febrile neutropenia, dose reductions, or lengthy dose delays) may have had significant negative effects on quality of life or even response to treatment.

It has been more than 15 years since the initial approval of myeloid growth factors to reduce febrile neutropenia in cancer patients receiving myelosuppressive chemotherapy.[1] As with other novel therapeutics, the approval of filgrastim (Neupogen) did not mark the end of research in this area, but rather the beginning.

Anemia is common in many patients with cancer treated with chemotherapy. One option for managing chemotherapy-induced anemia (CIA) is erythropoiesis-stimulating proteins (ESPs), which are indicated for the treatment of CIA in patients with most types of cancer. They have been shown to be safe and effective in numerous well-documented studies, and their side effects are well known. The rate of thrombotic events with the long-acting ESP darbepoetin alfa (Aranesp) has been consistent in studies conducted before and after its approval. The association of thrombotic events with high hemoglobin levels or rapid increases in its levels in patients with cancer remains controversial. Adjusting the dose of the ESP to maintain and monitor a target hemoglobin level of 11 to 12 g/dL is certainly prudent and may help prevent or minimize these events. Chemotherapy-induced anemia has been associated with shorter survival in patients with cancer, and the relation is likely multifactorial. Data on the treatment of CIA with ESPs have not shown a consistent effect on survival. Two studies in patients with hemoglobin levels above the target level showed that survival was shorter in the patients treated with ESPs. A review of data from other trials found no effect of ESPs on survival, and other trials suggested a positive effect. This article reviews data on survival in patients treated with ESPs and discusses five large randomized controlled trials of darbepoetin alfa that are addressing this issue.

Neutropenia is the primary dose-limiting toxicity in patients with cancer treated with systemic chemotherapy. The risk of febrile neutropenia (FN) has been estimated on the basis of the chemotherapy regimen, but studies are now finding a number of patient-related and disease-related risk factors for FN and other complications, such as hospitalization, chemotherapy dose reductions and delays, and mortality. These patient-related risk factors have been incorporated into clinical guidelines for managing neutropenia. The newly released guidelines on the use of myeloid growth factors with cancer chemotherapy of the National Comprehensive Cancer Network use disease- and patient-related factors along with the chemotherapy regimen risk. These guidelines also differ from previous guidelines in that they recommend the routine use of colony-stimulating factors (CSFs) in patients in whom the risk of neutropenia is > 20% (the previous threshold was ≥ 40%); this recommendation is based on recent data that show the clinical benefits of filgrastim (Neupogen) and pegfilgrastim (Neulasta) in studies in which the overall populations had FN risks of between 20% and 40%. The use of guidelines such as these in clinical practice will make it possible to target CSFs to appropriate patients in the first cycle of chemotherapy, when the risk of neutropenia is highest.

Chemotherapy-induced neutropenia (CIN) is the primary dose-limiting toxicity in patients being treated for cancer. The substantial toll of CIN includes febrile neutropenia (FN), hospitalization, infection, early mortality, increased medical costs, decreased quality of life, and the potential for diminished long-term survival due to chemotherapy dose reductions and delays.

For years, chemotherapy-associated myelosuppression has represented a majorlimitation to a patient’s tolerance of anticancer therapy. In addition, theclinical consequences of chemotherapy-induced myelosuppression (such as febrileneutropenia, dose reductions, or lengthy dose delays) may have had significantnegative effects on quality of life or even response to treatment.

There has been a remarkable explosion in medicalinformation over the past several years.The rate of new discoveries and improved understandingof the biology and treatment ofcancer is ever-increasing. The same is true inthe area of supportive cancer therapy.[1]

The clinical development of recombinant human erythropoietin (rHuEPO) has had a remarkable impact on the clinical practice of oncology. A decade ago, randomized, placebo-controlled trials in anemic cancer patients demonstrated that rHuEPO resulted in an improvement in hemoglobin and hematocrit, a reduction in transfusion requirements, and improvement in quality-of-life (QOL) end points. Based on these trials, recombinant erythropoietin was approved for the treatment of anemia in patients with nonmyeloid malignancies in whom the anemia was caused by the effect of chemotherapy.

During the 1980s, platinum-based regimens were yielding response rates typically less than 25%, median survival durations of about 25 weeks, and 1-year survival rates less than 25% in patients with advanced non-small-cell lung

Randomized trials in patients with advanced non-small-cell lung cancer (NSCLC) have demonstrated that the combination of vinorelbine (Navelbine) and cisplatin

Docetaxel (Taxotere) hasdemonstrated significant activity as a single agent in the treatment of