To test the feasibility of accelerated interrupted twice-daily radiation and concurrent cisplatin administration in patients with locally advanced head and neck cancer.
Patients and Methods
Nineteen patients with locally advanced head and neck cancer were treated with accelerated bifractionated radiation with concurrent administration of cisplatin. There were 18 men and 1 female with a median age of 60 years (range, 17–71) and median performance status of 90 (-range, 80–100). Sixteen patients (85%) presented with stage IV disease. Primary site included the nasopharynx (n = 7), oropharynx (n = 5), hypopharynx (n = 1) and larynx (n = 6). Radiation consisted of two fractions of 1.6 Gy each daily, five times weekly to a total dose of 64 Gy. Cisplatin was administered at a dose of 100 mg/m2 on days 2 and 28 of the treatment period.
Results
Nine patients achieved a complete response (47%; 95% CI, 25%–70%) and 5 a partial response (26%; 95% CI, 7%–46%). Grade III–IV toxicity included leukopenia (16%), mucositis (26%), dry mouth (5%), weight loss (16%) and infection (5%). After a median follow-up of 27.11 months (range, 1–33+), 9 patients have died. Median time to progression was 11 months (range, 1–32+) and median survival 25 months (range, 1–32+).
Conclusions
Accelerated twice-daily radiation with concurrent cisplatin is effective in locally advanced head and neck cancer and can be safely given with manageable toxicity.
Al-SarrafM., PajakT.F., MarcialV.A., MowryP., CooperJ.S., StetzJ., EnsleyJ.F., Velez-GarciaE.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. Cancer, 29: 259–265, 1987.
2.
BeggA.C.: Cisplatin and radiation: interaction probabilities and therapeutic possibilities. Int. J. Radiat. Oncol. Biol. Phys., 19: 1183–1189, 1990.
3.
BensadounR.J., ChauvelP., DassonvilleO., LaudoyerY., BourdinS., PrevostB., ResbeutM., SchneiderM., DemardF.: Results of a multicentric phase II study for the treatment of locally advanced inoperable pharyngeal carcinomas with continuous bifractionated radiotherapy and concomitant CDDP-5FU chemotherapy (Abst.). Proc. Am. Soc. Clin. Oncol., 14: 293, 1995.
4.
CoughlinC.T., RichmondR.C.: Platinum based combined modality approach for locally advanced head and neck carcinoma. Int. J. Radiat. Oncol. Biol. Phys., 11: 915–919, 1985.
5.
CoxJ.D., PajakT.F., MarcialV.A., HanksG.E., MohiuddiM., FuK.K., ByhardtR.W., RubinP.: Dose-response for local control with hyperfractionated radiation therapy in advanced carcinomas of the upper aerodigestive tracts: preliminary report of Radiation Therapy Oncology Group Protocol 83–13. Int. J. Radiat. Oncol. Biol. Phys., 18: 515–521, 1990.
6.
DoupleE.B., RichmondR.C., O'HaraJ.A., CoughlinC.T.: Carboplatin as a potentiator of radiation therapy. Cancer Treat. Rev., 12 (Suppl A): 111–124, 1985.
7.
DragovicJ., DoyleT.J., TilchenE.J., NicholsR.D., BenningeM.S., CarlsonE.R., BoydS.B., JacobsenG.R.: Accelerated fractionation radiotherapy and concomitant chemotherapy in patients with stage IV inoperable head and neck cancer. Cancer, 76: 1655–1661, 1995.
8.
FountzilasG., SkarlosD., KosmidisP., SamantasE., Kalogera-FountzilaÁ., PapaspyrouP., TzitzikasJ., SridharK.S., MakrantonakisP., PantelakosP., NikolaouA., BacoyiannisH., SinodinouM., BanisC., DaniilidisJ.: Radiation therapy and concurrent cisplatin administration in locally advanced head and neck cancer. Acta. Oncol., 33: 825–830, 1994.
9.
FowlerJ.F.: Potential for increasing the differential between tumors and normal tissues: can proliferation rate be used? Int. J. Radiat. Oncol. Biol. Phys., 12: 641–645, 1986.
10.
GaspariniG., RecherG., TestolinA., Dal FiorS., PanzoniG.A., CristoferiV., SquaquaraR., PozzaF.: Synchronous radiotherapy and chemotherapy with cisplatin in the management of locally advanced or recurrent head and neck cancer. Am. J. Clin. Oncol., 15: 242–249, 1992.
11.
HigiM., HeuserL., SchmidtC., GrunD., SchettleD., SchmittG.: Simultaneous cisplatin and radiotherapy of locally advanced squamous cell carcinomas of the head and neck region. A clinical pilot study. Dtsch. Med. Wochenschr., 108: 1743–1745, 1983.
12.
KaplanE.L., MeierP.: Non parametric estimation for incomplete observations. J. Am. Stat. Assoc., 53: 457–481, 1958.
13.
KarstensJ.H., HermesH., SchnarkowskiP., AmmonJ.: Accelerated fractionated irradiation with simultaneous cisplatin infusion in advanced head and neck cancer. Onkologie, 12: 187–189, 1989.
14.
LambD.S., SpryN.A., GrayA.J., JohnsonA.D., AlexandeS.R., DallyM.J.: Accelerated fractionation radiotherapy for advanced head and neck cancer. Radiother. Oncol., 18: 107–116, 1990.
15.
LeipzigB., WestmoreS.J., PutzeysR., SuenJ.Y., SnydermaN.L.: Cisplatin potentiation of radiotherapy: long-term follow-up. Arch. Otolaryngol. Head Neck Surg., 111: 114–118, 1985.
16.
McDonaldS., MillsE.E.D., Van der MerweA.M., RubinP., LushC.M.: Simultaneous radiation therapy and cisplatin chemotherapy in advanced cancer of the head and neck. Am. J. Clin. Oncol., 10: 410–416, 1987.
17.
MaciejewskiB., WithersH.R., TaylorJ.M., HliniakA.: Dose fractionation and regeneration in radiotherapy for cancer of the oral cavity and oropharynx: tumor dose-response and repopulation. Int. J. Radiat. Oncol. Biol. Phys., 16: 831–843, 1989.
18.
MarcialV.A., PajakT.F., MohiuddinM., CoopperJ.S., Al SarrafM., MowryP.A., CurranW., CrissmanJ., RodriguezM., GarciaE.V.: Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Long-term results of the Radiation Therapy Oncology Group study 81-17. Cancer, 66: 1861–1868, 1990.
19.
O'HaraJ.A., DoupleE.B., RichmondR.C.: Enhancement of radiation-induced cell kill by platinum complexes (carboplatin and iproplatin) in V79 cells. Int. J. Radiat. Oncol. Biol. Phys., 12: 1419–1422, 1986.
20.
ParsonsJ.T., MendenhallW.M., StringerS., CassiniN.J., MillionR.: Twice-a-day radiotherapy for squamous cell carcinoma of the head and neck: The University of Florida experience. Head Neck, 15: 87–96, 1993.
21.
SaundersM.I., DischeS., HongA., GroschE.J., FermontD.C., AshfordR.F.U., MaherE.J.: Continuous hyperfractionated accelerated radiotherapy in locally advanced carcinoma of the head and neck region. Int. J. Radiat. Oncol. Biol. Phys., 17: 1287–1293, 1989.
22.
SchnabelT., ZamboglouN., KolotasC., HartmannA., SchmittG.: Combined radiotherapy with carboplatin in the treatment of advanced head and neck carcinomas. Oncology50 (Suppl 2): 16–22, 1993.
23.
SondermanN.L., WestmoreS.J., SuenJ.Y.: Cisplatin sensitization to radiotherapy in stage IV squamous cell carcinoma of the head and neck. Arch. Otolaryngol. Head Neck Surg., 112: 1147–1150, 1986.
24.
ViuramB., StrongE.W., ShahJ.P., SpiroR.: Failure at distant sites following multimodality treatment for advanced head and neck cancer. Head Neck Surg., 6: 730–733, 1984.
25.
WangC.C.: Accelerated hyperfractionation radiation therapy for carcinoma of the nasopharynx. Techniques and results. Cancer, 63: 2461–2467, 1989.
26.
WangC.C., SuitH.D., BlitzerP.H.: Twice-a-day radiation therapy for supraglottic carcinoma. Int. J. Radiat. Oncol. Biol. Phys., 12: 3–7, 1986.
27.
WithersH.R., TaylorJ.M.G., MaciejewskiB.: The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta. Oncol., 27: 131–146, 1988.
28.
ZamboglouN., AchterrathW., SchnabelT.H., LenazL., KolotasC., SchmittG.: Simultaneous radiotherapy and chemotherapy with carboplatin in inoperable squamous cell carcinoma of the head and neck: a phase II study. Cancer Invest., 10: 349–355, 1992.
