Chemotherapy dose intensity

After a meticulous review of the biomedical literature, the panel concluded that routine use of colony-stimulating factors for primary prophylaxis of febrile neutropenia in previously untreated patients is not justified by existing data. There is evidence, however, that colony-stimulation factor administration can decrease the probability of febrile neutropenia in subsequent cycles of chemotherapy after a documented occurrence in an earlier cycle. However, dose reduction after a severe episode, rather than administration of colony-stimulating factors, should be considered as a primary therapeutic option. In the absence of clinical evidence or other compelling reasons to maintain chemotherapy dose intensity, physicians should consider chemotherapy dose reduction... 

After completion of induction and restoration of normal hematopoiesis, patients begin intensification (consolidation). The goal of intensification is to administer dose-intensive chemotherapy in an effort to further reduce the burden of... 

Poor performance status Planned full dose intensity of chemotherapy... 

Adjuvant chemotherapy can cause substantial toxicity. Because maintaining dose intensity is important in cure of disease, supportive care should be optimized with measures such as antiemetics and growth factors. 

GM-CSF was approved in 1991 by the United States Food and Drag Administration (FDA) to support transplant associated neutropenia and mobilize stem cells. In Europe, it is also approved for prophylactic treatment following dose intensive chemotherapy. However, the rate of absolute neutrophil count (ANC) recovery in response to treatment with GM-CSF in patients receiving myelosuppressive chemotherapy or in the... 

Filgrastim is used in conjunction with cancer chemotherapy in one of two ways prophylactic administration aims to prevent onset of neutropenia in the first place, while therapeutic administration aims to reverse neutropenia already established. It is generally effective in both circumstances and in clinical trials it was found to reduce the number of (neutropenia-induced) days of patient hospitalization by up to 50%. Filgrastim administration may also permit modest increases in the maximum dose intensity utilizable in chemotherapeutic regimes. 

Neutropenia is a common adverse effect of the cytotoxic drugs used to treat cancer and increases the risk of serious infection in patients receiving chemotherapy. Unlike the treatment of anemia and thrombocytopenia, transfusion of neutropenic patients with granulocytes collected from donors is performed rarely and with limited success. The introduction of G-CSF in 1991 represented a milestone in the treatment of chemotherapy-induced neutropenia. This growth factor dramatically accelerates the rate of neutrophil recovery after dose-intensive myelosuppressive chemotherapy (Figure 33-5). It reduces the duration of neutropenia and usually raises the nadir count, the lowest neutrophil count seen following a cycle of chemotherapy. 

Issac C, Robert NJ, Bailey FA, Schuster MW, et al. 1997. Randomized placebo-controlled study of recombinant human interleukin 11 to prevent chemotherapy induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol. 15 3368-3377. 

Available data suggest that the antitumor therapeutic response of older patients is optimal when exposure to appropriate chemotherapy is the same as for younger patients. For example, the treatment of non-HodgkiiVs lymphoma with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or etoposide, mitoxantrone, and prednimustine (VMP) is less effective in older patients when dose reductions are made (73, 74). Similarly, treatment of metastatic breast cancer in younger and older patients with the same dose intensity of doxorubicin-based chemotherapy resulted in similar outcomes as measured by time to progression of disease and overall survival (75). 

Lyman GH, Kuderer NM, Djulbegovic B. Prophy-latic granulocyte colony-stimulating factor in patients receiving dose-intensive cancer chemotherapy A meta-analysis. Am J Med 2002 112 406-11. 

In those tumours where cures can be achieved by chemotherapy (acute lymphoblastic leukaemia in childhood, Hodgkin s lymphoma, choriocarcinoma) it is essential that optimal doses of chemotherapy be administered and dose intensity maintained in order to avoid the emergence of chemoresistance. 

Green M. Dose-intensive chemotherapy with cytokine support. Semin Oncol 1994 21(1 Suppl l) l-6. 

Tolcher AW, Giusti RM, O Shaughnessy JA, Cowan KH. Arterial thrombosis associated with granulocyte-macro-phage colony-stimulating factor (GM-CSF) administration in breast cancer patients treated with dose-intensive chemotherapy a report of two cases. Cancer Invest 1995 13(2) 188-92. 

Piccart MJ, Biganzoh L, Di Leo A. The impact of chemotherapy dose density and dose intensity on breast cancer outcome what have we learned Eur J Cancer 2000 36(Suppl 1) S4-S 10. 

Wood WC, Budman DR, Korzun AH, et al. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. NEnglJMed 1994 18 1253-1259. 

Dose intensity can be increased by shortening the interval between cycles (i.e., dose density). The data with dose-dense chemotherapy regimens is conflicting, with findings of both no survival difference and improved survival with dose-dense regimens. " ... 

Hryniuk W, Bush H. The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol 1984 2 1281-1288. 

Klasa RJ, Murray N, Goldman AJ. Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung. J Clin Oncol... 

I New Chemotherapy Regimens. More recently, new regimens have been developed with increased dose-intensity or dose-density. Two relatively new regimens (BEACOPP and Stanford V) are variations of the above hybrid regimens that administer drugs with a shorter frequency or have escalated the dose of the most active agents. Since the majority of patients in the recent trials also received radiation therapy, results of these promising new trials are discussed in the next section. 

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