Dose-Dense Chemotherapy

Author: OncoLink Team
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What is chemotherapy?

Tumor cells, which make up cancer, grow and reproduce (multiply) very quickly. Normal, healthy cells know to stop reproducing and growing when they touch other cells. Cancer cells keep growing, not knowing when to stop. RNA and DNA in the cell tell it how to grow and reproduce. These cancer cells go through a cycle, made up of phases. As the cancer cells complete a cycle, more cancer cells are made. Chemotherapy is a type of medicine that is used to attack these cancer cells. Chemotherapy hurts the RNA or DNA, which stops the cancer from growing. Chemotherapy is called a “systemic” therapy. This means that it travels throughout the whole body to kill cells. A regimen is a combination of chemotherapy medications given to treat certain types of cancer.

What is dose-dense chemotherapy?

Dose-Dense Chemotherapy (DDC) is a way to give chemotherapy regimens more frequently than normally scheduled, with less time between doses. DDC hopes to kill as much of the tumor as possible. The actual dose of chemotherapy is not increased, but the time between doses is shortened. By giving the same doses of chemotherapy more frequently, the chemotherapy interrupts the rapid growth phase of the tumor cells. Thus, the medications hit the tumor cells at the time when they are just beginning to grow rapidly again. In other words, "hit them while they are down." This model was called the Norton-Simon model, after the researchers who first described it.

A concern of DDC is that giving chemotherapy more frequently would lead to low white blood counts and infection. Through the use of growth factors (NeupogenNeulastaLeukine), we are able to have faster recovery of white blood cells, decreasing the chance of infection. Several DDC studies have shown a higher incidence of anemia (low red blood cell count) and bone pain (likely related to the use of a growth factor) with these regimens, but the DDC regimens also mean a decrease in the length of therapy by 4-6 weeks.

What types of cancer is DDC used in?

Studies have found that premenopausal women with high-risk disease (hormone receptor-negative, Her2 positive, and lymph node positive) see the greatest benefit from DDC in breast cancer treatment. These studies have shown improvement in ten-year survival in premenopausal patients with hormone receptor-positive tumors by 22%, and by 35% in those with hormone receptor-negative tumors. This study also found that the use of DDC does not seem to be linked with an increased risk of developing treatment-induced menopause or amenorrhea (absence of menstrual periods). This is an important finding because early menopause will lead to loss of ovarian function, which can increase the risk of osteoporosis and early heart disease. In addition, early menopause can result in infertility, hot flashes, vaginal dryness and weight gain, all of which can have a negative psychosocial, emotional, and physical impact on women of childbearing age.

DDC has become a standard of care for the treatment of some high-risk lymphomas. Studies are continuing to evaluate DDC used with rituximab. Studies have also evaluated using DDC in ovarian cancer, with positive results.

It is clear that there is a benefit to DDC for some patients. Deciding who will benefit is the focus of ongoing studies in these and other types of cancer. In addition, longer follow-up of previously reported studies will give more information on the use of DDC and long-term benefits or complications.

If your treatment plan includes dose-dense chemotherapy, talk with your care team about any concerns you may have.

References

Brusamolino E, Rusconi C, Montalbetti L, Gargantini L, Uziel L, Pinotti G, Fava S, Rigacci L, Pagnucco G, Pascutto C, Morra E, Lazzarino M. Dose-dense R-CHOP-14 supported by pegfilgrastim in patients with diffuse large B-cell lymphoma: a phase II study of feasibility and toxicity. Haematologica. 2006 Apr; 91(4):496-502.

Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; Southwest Oncology Group. Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol. 2003 Jul 1; 21(13):2466-73.

Cunningham et al. A phase III trial comparing R-CHOP 14 and R-CHOP 21 for the treatment of patients with newly diagnosed diffuse large B-cell non-Hodgkin's lymphoma. J Clin Oncol 27:15s, 2009 (suppl; abstr 8506).

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Gregory SA. Trumper L. Chemotherapy dose intensity in non-Hodgkin's lymphoma: is dose intensity an emerging paradigm for better outcomes? Annals of Oncology 2005:16(9):1413-24.

Katsumata N. et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1331-8. Epub 2009 Sep 18.

Kummel S et al. Dose-dense chemotherapy for primary breast cancer.

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Kummel S. et al. Randomised trial: survival benefit and safety of adjuvant dose - dense chemotherapy for node-positive breast cancer. British Journal of Cancer 2006:94(9):1237-44.

Lin NU, Gelman R, Winer EP. Dose Density in Breast Cancer: A Simple Message? J Natl Cancer Inst 2005;97:1712-1714.

Norton L. Conceptual and practical implications of breast tissue geometry: toward a more effective, less toxic therapy. Oncologist. 2005;10:370-381.

Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rube C, Loeffler M. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL -B1 trial of the DSHNHL. Blood. 2004 Aug 1; 104(3):626-33.

Seidman AD. Current status of dose - dense chemotherapy for breast cancer. Cancer Chemotherapy & Pharmacology 2005: 56 Suppl 1:78-83.

Untch M. et al. Dose-dense sequential epirubicin-paclitaxel as preoperative treatment of breast cancer: results of a randomized trial AGO study (abstract 133). Proc Am Soc Clin Oncol 2005: 21:34A.

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