A retrospective analysis was conducted to evaluate the tolerability as well as the impact of concurrent adjuvant CMF chemotherapy and radiation therapy on total CMF dose and dose intensity.
Methods
The medical records of 59 patients who had received conservative or radical surgery for breast cancer were analyzed. All patients had been assigned to 6 cycles of “1,8 CMF” adjuvant chemotherapy and concomitant radiation therapy. Total drug dose and dose intensity were calculated. Toxicity was recorded scored according to WHO criteria.
Results
A total of 355 cycles was administered. Fifty of 59 patients received at least 85% of the programmed chemotherapy total dose, the median value being 100% (range, 42-100). The median relative dose intensity was 0.97 (range, 0.42-1.01). Forty-four of 59 (75%) patients experienced grade 3-4 neutropenia (20 febrile neutropenia) and 29 (49%) required G-CSF support.
Conclusions
This retrospective analysis showed that it is possible to give concurrent CMF and breast radiation while ensuring adequate chemotherapy total doses and dose intensities to most patients. However, G-CSF support is required in a significant proportion of patients.
Early Breast Cancer Trialists’ Collaborative Group:Poly-chemotherapy for early breast cancer: an overview of the randomised trials.Lancet, 352: 930–942, 1998.
2.
CuzickJ., StewartH., RutqvistL., HoughtonJ., EdwardsR., RedmondC., PetoR., BaumM., FisherB., and HostH.: Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy.J Clin Oncol, 12: 447–453, 1994.
3.
OvergaardM., HansenP.S., OvergaardJ., RoseC., AnderssonM., BachF., KjaerM., GadebergC.C., MouridsenH.T., JensenM.B., ZedelerK.: Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy.N Engl J Med, 337: 949–955, 1997.
4.
RagazJ., JacksonS.M., LeN., PlenderleithI.H., SpinelliJ.J., BascoV.E., WilsonK.S., KnowlingM.A., CoppinC.M.L., ParadisM., ColdmanA.J., OlivottoI.A.: Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer.N Engl J Med, 337: 956–962, 1997.
5.
UngO., LanglandsA.O., BarracloughB., BoyagesJ.: Combined chemotherapy and radiotherapy for patients with breast cancer and extensive nodal involvement.J Clin Oncol, 13: 435–443, 1995.
6.
GoldhirschA., GlickJ.H., GelberR.D., CoatesA.S., SennH.J.: Meeting highlights: International Consensus Panel on the Treatment of Primary Breast Cancer.J Clin Oncol, 19: 3817–3827, 2001.
7.
SlotmanB.J., MeyerO.W., NjoK.H., KarimA.B.: Importance of timing of radiotherapy in breast conserving treatment for early stage breast cancer.Radiother Oncol, 30: 206–212, 1994.
8.
PronzatoP., CamporaE., AmorosoD., BertelliG., BottoF., ConteP.F., SertoliM.R., RossoR.: Impact of administration-related factors on outcome of adjuvant chemotherapy for primary breast cancer.Am J Clin Oncol, 12: 481–485, 1989.
9.
HartsellW.F., RecineD.C., GriemK.L., MurthyA.K.: Delaying the initiation of intact breast irradiation for patients with lymph node positive breast cancer increases the risk of local recurrence.Cancer, 76: 2497–2503, 1995.
10.
ColleoniM., BonettiM., CoatesA.S., Castiglione-GertschM., GelberR.D., PriceK., RudenstamC.M., LindtnerJ., CollinsJ., ThürlimannB., HolmbergS., VeronesiA., MariniG., GoldhirschA. for the International Breast Cancer Study Group: Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors.J Clin Oncol,18: 584–590, 2000.
11.
RechtA., ComeS.E., HendersonI.C., GelmanR.S., SilverB., HayesD.F., ShulmanL.N., HarrisJ.R.: The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer.N Engl J Med, 334: 1356–1361, 1996.
12.
LawrenceT.S., TepperJ.E., BlackstockA.W.: Fluoropyrimidine-radiation interactions in cells and tumors.Semin Radiat Oncol, 7: 260–266, 1997.
13.
RichT.A.: Irradiation plus 5-fluorouracil: cellular mechanisms of action and treatment schedules.Semin Radiat Oncol, 7: 267–273, 1997.
14.
BonadonnaG., ValagussaP.: Dose-response effect of adjuvant chemotherapy in breast cancer.N Engl J Med, 304: 10–15, 1981.
15.
BonadonnaG., ValagussaP., MoliterniA., ZambettiM., BrambillaC.: Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up.N Eng J Med, 332: 901–916, 1995.
16.
HryniukW., LevineM.N.: Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer.J Clin Oncol, 4: 1162–1170, 1986.
17.
WoodW.C., BudmanD.R., KorzunA.H., CooperM.R., YoungerJ., HartR.D., MooreA., EllertonJ.A., NortonL., FerreeC.R., Bal-lowA.C., FreiE., Craig HendersonI.: Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma.N Engl J Med, 330: 1253–1259, 1994.
18.
BudmanD.R., BerryD.A., CirrincioneC.T., HendersonI.C., WoodW.C., WeissR.B., FerreeC.R., MussH.B., GreenM.R., NortonL., FreiE.: Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B.J Natl Cancer Inst, 19: 1205–1211, 1998.
19.
French Adjuvant Study Group:Benefit of high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results from French Adjuvant Study Group 05 randomized trial.J Clin Oncol, 19: 602–611, 2001.
20.
LevineJ.F., ColemanC.N., CoxR.S., RayG.R., RogowayW.M., MartinezA., StockdaleF.E.: The effect of postoperative and primary radiation therapy on delivered dose of adjuvant cyclophosphamide, methotrexate and fluorouracil (CMF) chemotherapy in breast cancer.Cancer, 53: 237–241, 1984.
21.
BanerjeeT.K., HoehnJ.L., GreenlawR.H., JacobyC.: Chemotherapy drug dose alteration due to radiation therapy in adjuvant situation in breast cancer.J Clin Oncol, 7: 437–442, 1984.
22.
FisherB., BrownA., MamounasE., WieandS., RobidouxA., MargoleseR.G., CruzA.B.Jr., FisherE.R., WickerhamD.L., Wol-markN., DeCillisA., HoehnJ.L., LeesA.W., DimitrovN.V.: Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15.J Clin Oncol, 8: 1483–1496, 1990.
23.
De GraafH., WillemseP.H., BongS.B., PiersmaH., TjabbesT., van VeelenH., CoenenJ.L., de VriesE.G.: Dose intensity of standard adjuvant CMF with granulocyte colony-stimulation factor from premenopausal patients with node-positive breast cancer.Oncology, 53: 289–294, 1996.
24.
LambD., AtkinsonC., JosephD., O'BrienP., AcklandS., BonaventuraA., DadyP., HamiltonC., SpryN., StewartJ., Den-hamJ.: Simultaneous adjuvant radiotherapy and chemotherapy for stage I and II breast cancer.Australas Radiol, 43: 220–226, 1999.
25.
DubeyA., RechtA., ComeS.E., GelmanR.S., SilverB., HarrisJ.R., ShulmanL.N.: Concurrent CMF and radiation therapy for early stage breast cancer: results of a pilot study.Int J Radiol Oncol Biol Phys, 45: 877–884, 1999.
26.
IsaacN., PanzarellaT., LauA., MayersC., KirkbrideP., Tan-nockI.F., VallisK.A.: Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for breast carcinoma: a well tolerated adjuvant regimen.Cancer, 95: 696–703, 2002.
