The aim of the study was to assess the activity and the toxicity of cisplatin (DDP) and fluorouracil (FU) administered by continuous infusion as neoadjuvant chemotherapy for patients with stage II-IV, MO squamous cell carcinoma of the head and neck.
Methods
Thirty previously untreated patients were submitted to chemotherapy with DDP (20 mg/m2) and FU (1000 mg/m2), both in continuous infusion for 5 days, repeated every 21 days, for a maximum of 5 cycles. Following completion of chemotherapy, the patients underwent radiotherapy; in some patients surgery was performed immediately after chemotherapy. All patients were monitored for response, time to failure, survival, treatment-related events and toxicity.
Results
All patients were evaluated for response; after chemotherapy the complete response rate was 27% and the partial response rate 33%. Twenty-four patients underwent radiotherapy: the overall response rate was 83% (complete response 79%). After a median follow-up of 34 months, the median survival time was 22 months with a median time to failure of 15 months. Acute vascular accidents were the main and unexpected adverse events, with 2 deaths for pulmonary embolism and 1 for stroke. The response rate to the regimen does not seem to be better than that obtained with the standard combination of cisplatin bolus and fluorouracil continuous infusion. The disadvantage of the regimen is that it causes more discomfort for the patient in that it requires hospitalization.
Conclusions
For this reason, we believe that there are no elements for recommending the schedule as neoadjuvant treatment of patients with squamous cell carcinoma of the head and neck or as an experimental arm in a randomized trial.
BernalA.G., CruzJ.J., SanchezP., MunozA., NietoA., FonsecaE., CalleR., GomezJ.L.: Four-day continuous infusion of cisplatin and 5-fluorouracil in head and neck cancer.Cancer, 63: 1927–1930, 1989.
CarugatiA., PradierR., De la TorreA.: Combination chemotherapy pre radical treatment for head and neck squamous cell carcinoma (Abst.).Proc. Am. Soc. Clin. Oncol., 7: 589, 1988.
5.
ClarkJ.R., FallonB.G., FreiE.III: Induction chemotherapy as initial treatment for advanced head and neck cancer: a model for the multidisciplinary treatment of solid tumor.In: Important Advances in Oncology, DeVitaV.T.Jr., HellmanS., RosenbergS.A. (Eds.), p. 175–195, J.B. Lippincott, Philadelphia, 1987.
6.
ClarkJ.R., FreiE.III: Chemotherapy for head and neck cancer: progress and controversy in the management of patients with MO disease.Semin. Oncol., 16: 44–57, 1989.
7.
De ContiR.C., ToftnessB.R., LangeR.C.: Clinical and pharmacological studies with cis-dichlorodiammineplatinum (II).Cancer Res., 33: 1310–1315, 1973.
DrewinkoB., BrownB.W., GottliebJ.A.: The effect of cis-diamminedichloroplatinum (II) on cultured human lymphoma cells and its therapeutic implication.Cancer Res., 33: 3091–3095, 1973.
10.
DreyfussA.I., ClarkJ.R., WrightJ.E., NorrisC.M.Jr., BusseP.M., LucariniJ.W., FallonB.G., CaseyD., AndersenJ.W., KleinR., RosowskyA., MillerD., FreiE.III: Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck.Ann. Intern. Med., 112: 167–172, 1990.
11.
EdwardsG.S., LaneM., SmithF.E.: Long-term treatment with cis-dichlorodiammineplatinum (II), vinblastine, bleomycin: possible association with severe coronary artery disease (Letter). Cancer Treat.Rep., 63: 551–552, 1979.
12.
EnsleyJ., KishJ., TapazoglouE., JacobsJ., WeaverA., Ma-thogR., Al-SarrafM.: Continued intensification of an alternating induction regimen in patients with advanced, untreated squamous cell carcinoma of head and neck (Abst.).Proc. Am. Soc. Clin. Oncol., 7: 598, 1988.
13.
ErvinT.J., ClarkJ.R., WeichselbaumR.R., FallonB.G., MillerD., FabianR.L., PosnerM.R., NorrisC.M.Jr., TuttleS.A., SchoenfeldD.A.: An analysis of induction and adjuvant chemotherapy in the mutlidisciplinary treatment of squamous-cell carcinoma of head and neck.J. Clin. Oncol., 5: 10–20, 1987.
14.
ForastiereA.A., BelliveauJ.F., GorenM.P.: A pharmacokinetic and toxicity evaluation of continuous versus bolus cisplatin in head and neck cancer patients.In: Proceedings of the Second International Head and Neck Oncology Research Conference, VA, September 10-12, 1987.
15.
ForastiereA.A., BelliveauJ.F., GorenP.G., VogelW.C., PosnerM.R., O'LearyG.P.Jr.: Pharmacokinetic and toxicity evaluation of five-days continuous infusion versus intermittent bolus cis-diamminedichloroplatinum (II) in head and neck cancer patients.Cancer Res., 48: 3869–3874, 1988.
16.
ForastiereA.A., MetchB., SchullerD.E., EnsleyJ.F., HutchinsL.F., TriozziP., KishJ.A., McClureS., VonFeldtE., WilliamsonS.K., Von HoffD.D.: Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamuos-cell carcinoma of head and neck: a Southwest Oncology Group study.J. Clin. Oncol., 10: 1245–1251, 1992.
17.
Head and Neck Contracts Program:Adjuvant chemotherapy for advanced head and neck squamous carcinoma. Final report of the Head and Neck Contracts Program.Cancer, 60: 301–311, 1987.
18.
JacobsC.: The internist in the management of head and neck cancer.Ann. Intern. Med., 113: 771–778, 1990.
19.
JacobsC., LymanG., Velez-GarciaE., SridharK.S., KnightW., HochsterH., GoodnoughL.T., MortimerJ.E., EinhornL.H., SchacterL., CherngN., DaltonT., BurroughsJ., RozencweigM.: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck.J. Clin. Oncol., 10: 257–263, 1992.
KiesM.S., GordonL.I., HauckW.W., KrespiY., OssofR.H., PecaroB.C., YuskaC., LamutC.H., BrandW.N., ChangS.K.: Analysis of complete responders after initial treatment with chemotherapy in head and neck cancer.Otolaryngol. Head Neck Surg., 93: 199–205, 1985.
22.
KishJ.A., EnsleyJ.F., JacobsJ., WeaverA., CummingsG., Al-SarrafM.: A randomized trial of cisplatin (CACP) + 5-fluorouracil (5-FU) infusion and CACP + 5-FU bolus for recurrent and advanced squamous cell carcinoma of the head and neck.Cancer, 56: 2740–2744, 1985.
23.
KishJ.A., EnsleyJ.F., JacobsJ.R., BinnsP., Al-SarrafM.: Evaluation of high-dose cisplatin and 5-FU as initial therapy in advanced head and neck cancer.Am. J. Clin. Oncol., 11: 553–557, 1988.
24.
KuklaL.J., McGuireW.P., LadT., SaltielM.: Acute vascular episodes associated with therapy for carcinomas of the upper aerodigestive tract with bleomycin, vincristine and cisplatin.Cancer Treat. Rep., 66: 369–70, 1982.
25.
KunL.E., ToohillR.J., HoloyeP.Y., DuncavageJ.A., ByhardtR.W., RitchP.S., GrossmanT.W., HoffmannR.G., CoxJ.D., MalinT.: A randomized study of adjuvant chemotherapy for cancer of the upper aerodigestive tract.Int. J. Radiat. Oncol. Biol. Phys., 12: 173–178, 1986.
26.
MartinM., MazeronJ.J., BrunB., VergnesL., LelievreG., FeuilladeF., JuvanonJ.M., HaddadE., Souchal DelacourI., PeynegreR.: Neoadjuvant polychemotherapy of head and neck cancer: results of a randomized study (Abst.).Proc. Am. Soc. Clin. Oncol., 7: 590, 1988.
27.
MillerA.B., HoogstratenB., StaguetM.: Reporting results of cancer treatment.Cancer, 47: 207–214, 1981.
28.
MonkM.R., SanchezJ.D., PhelpsC.D.: Myocardial ischemia with fluorouracil and floxuridine therapy.Clin. Pharmacol., 6: 659–661, 1987.
29.
PennacchioJ.L., HongW.K., ShapshayS.: Combination of cisplatinum and bleomycin prior to surgery and/or radiotherapy compared with radiotherapy alone for the treatment of advanced squamous cell carcinoma of the head and neck.Cancer, 50: 2795–2801, 1982.
30.
PosnerM.R., SkarinA.T., ClarkJ., ErvinT.J.: Phase I study of continuous infusion cisplatin.Cancer. Treat. Rep., 70: 847–850, 1986.
31.
RooneyM., KishJ., JacobsJ., KinzieJ., WeaverA., CrissmanJ., Al SarrafM.: Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin.Cancer, 55: 1123–1128, 1985.
SalemP., KhalylM., JabbouryK., HashimiL.: Cis-diamminedichloroplatinum (II) by 5-day continuous infusion. A new dose schedule with minimal toxicity.Cancer, 53: 837–840, 1984.
34.
SchullerD.E., MetchB., SteinD.W., MattoxD., McCrackenJ.D.: Preoperative chemotherapy in advanced resectable head and neck cancer: final report of the Southwest Oncology Group.Laryngoscope, 98: 1205–1211, 1988.
35.
SidgestadC.P., GardinaD.J., PetersL.J.: Cell cycle phase preferential killing of fibrosarcoma tumor cells by cis-dichlo-rodiammineplatinum or Adriamycin (Abst.).Proc. Am. Assoc. Cancer. Res., 20: 178, 1979.
36.
StellP.M., DalbyJ.E., StricklandP.: Sequential chemotherapy and radiotherapy in advanced head and neck cancer.Clin. Radiol., 34: 463–467, 1983.
37.
ToohillR.J., AndersonT., ByhardtR.W., CoxJ.D., DuncavageJ.A., GrossmanT.W., HaasC.D., HaasJ.S., HartzA.J., LibnochJ.A.: Cisplatin and fluorouracil as neoadjuvant therapy in head and neck cancer: a preliminary report.Arch. Otolaryngol. Head Neck Surg., 113: 758–761, 1987.
38.
TupchongL., ScottC.B., BlitzerP.H., MarcialV.A., LowryL.D., JacobsJ.R., StetzJ., DavisL.W., SnowJ.B., ChandlerR., KramerS., PajakT.F.: Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03.Int. J. Radiat. Oncol. Biol. Phys., 20: 21–28, 1991.
39.
TurlapatyP.D., AlturaB.M.: Magnesium deficiency produces spasms of coronary arteries: relationship to etiology of sudden death ischemic heart disease.Science, 208: 198–200, 1980.
40.
UrbaS.G., ForastiereA.A.: Systemic therapy of head and neck cancer: most effective agents and areas of controversy.Oncology, 3: 79–88, 1989.
41.
VogelzandN.J., TorkelsonJ.L., KennedyB.J.: Hypomagnesemia, renal dysfunction, and Raynaud's phenomenon in patients treated with cisplatin, vinblastine, and bleomycin.Cancer, 56: 2765–70, 1985.
42.
VokesE.E.Head and neck cancer.In: Chemotherapy Source Book, PerryM.C. (Ed.), pp. 918–931, Williams and Wilkins, Baltimore, 1992.
43.
VokesE.E., MickR., LesterE.P.: Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution.J. Clin. Oncol., 9: 1376–1384, 1992.
44.
VokesE.E., WeichselbaumR.R., MickR., McEvillyJ.M., HarafD.J., PanjeW.R.: Favorable long-term survival following induction chemotherapy with cisplatin, fluorouracil, and leucovorin and concomitant chemoradiotherapy for locally advanced head and neck cancer.J. Natl. Cancer Inst., 84: 877–882, 1992.
45.
WeaverA., FlemingS., EnsleyJ., KishJ.A., JacobsJ., KinzieJ., CrissmanJ., Al SarrafM.: Superior clinical response and survival rates with initial bolus of cisplatin and 120 hour infusion of 5-fluorouracil before definitive therapy for locally advanced head and neck cancer.Am. J. Surg., 148: 525–529, 1984.
