Restricted accessResearch articleFirst published online 1991-10
Carboplatin,Continuous Infusion Fluorouracil and Mid-cycle High-dose Methotrexate as Initial Treatment in Patients with Locally Advanced Head and Neck Cancer
Forty-nine patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were treated with 3 cycles of induction chemotherapy prior to definitive local treatment (surgery and/or radiation therapy). Chemotherapy consisted of carboplatin 300 mg/m2 on day 1, fluorouracil 1000 mg/m2 daily as a continuous infusion on days 1 to 5 and high-dose methotrexate 1.2 g/m2 with leucovorin rescue on day 14. After completing the induction chemotherapy, 9 patients (18%) achieved a complete remission (CR), 26 (54 %) a partial remission (PR), 7 had stable disease and 7 a progression. The response rates increased to 53 % CR and 18 % PR following locoregional treatment. Survival at 12 months was 61 % and its actuarial probability at 24 months 31 %. Median time to progression was 14 months. Toxicity from chemotherapy was generally mild. Nausea was observed in 35 %, vomiting in 26 %, stomatitis in 57 %, anemia in 22 %, leukopenia in 36%, thrombocytopenia in 26% and diarrhea in 6% of the patients. In conclusion, the combination of carboplatin, 5-day continuous-infusion fluorouracil and mid-cycle high-dose methotrexate is a moderately effective, well tolerated regimen in patients with SCCHN but does not seem superior to the combination of carboplatin and fluorouracil only.
Get full access to this article
View all access options for this article.
References
1.
American Joint Committee on Cancer: Manual for Staging of Cancer.3rd edition, pp. 27–51, J.B. Lippincott Co, Philadelphia, 1988.
2.
BasauriL.A., PousaA.L., SamperoF.: Carboplatin, an active drug in advanced head and neck cancer.Cancer Treat. Rep., 70: 1173–1176, 1986.
3.
BernalA.G., CruzG.G., SanchezP., MunozA., NietoA., FonsecaE., CalleR., GomezL.: Four-day continuous infusion of cisplatin and 5-fluorouracil in head and neck cancer.Cancer, 63: 1927–1930, 1989.
4.
ChristianM.C.: Carboplatin.Principles and Practice of Oncology Updates, 3: 1–16, 1989.
5.
ClavelM., CognettiF., DodionP., WildiersJ., RossoR., RossiA., GignouxB., Van RijmenantM., Cortes-FunesH., DalesioO.: Combination chemotherapy with methotrexate, bleomycin and vincristine with or without cisplatin in advanced squamous cell carcinoma of the head and neck.Cancer, 60: 1173–1177, 1987.
6.
EnsleyJ.F., JacobsJ.R., WeaverA., KinzieJ., CrissmanJ., CummingsG., Al-SarrafM.: Correlation between response to cisplatinum combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck.Cancer, 54: 811–814, 1984.
7.
EnsleyJ.F., KishJ., TapazoglouE., JacobsJ., WeaverA., AtkinsonD., AhmedK., MathogR., Al-SarrafM.: An intensive, five-course, alterating chemotherapy induction regimen used in patients with advanced unresectable head and neck cancer.J. Clin. Oncol., 6: 1147–1153, 1988.
8.
ErvinT.J., ClarkJ.R., WeichselbaumR.R.: Multidisciplinary treatment of advanced squamous cell carcinoma of the head and neck.Semin. Oncol., 12: 71–78, 1985.
9.
FazekasJ.T., SommerC., KramerS.: Adjuvant intravenous methotrexate or definitive radiotherapy alone for advanced squamous cell cancers of the oral cavity, oropharynx, supraglottic larynx or hypopharynx.Concluding report of an RTOG randomized trial of 639 patients. Int. J. Radiat. Oncol. Biol. Phys., 6: 533–541, 1980.
10.
FisherR.I., DeVitaV.T., HubbardS.M., LongoD.L., WesleyR., ChabnerB.A., YoungR.C.: Diffuse aggressive lymphomas: Increased survival after alternating flexible sequences of ProMACE and MOPP chemotherapy.Ann. Intern. Med., 98: 304–309, 1983.
11.
ForastiereA.A., NataleR.B., TakasugiB.J., CorenM.P., VogelW.C., Kudla-HatchV.: A phase I-II trial of carboplatin and 5-fluorouracil combination chemotherapy in advanced carcinoma of the head and neck.J. Clin. Oncol., 5: 190–196, 1987.
12.
FountzilasG., NicolaouA., SridharK., SiderasI., HaritantiA., AnastasakisC., DelisV., VritsiosA., DaniilidisJ.: Induction chemotherapy with cisplatinum, 5-fluorouracil, bleomycin, mitomycin C and hydroxyurea for previously untreated locally advanced squamous cell carcinomas of the head and neck.Arch. Otorhinolaryngol., 246: 373–377, 1989.
13.
MachinD., CampbellM.J.: Statistical Tables for the Design of Clinical Trials.Blackwell Scientific Publications, Oxford, 1987.
14.
OliverI.N., DalleyD., WoodsR., AroneyR., HughesR., BishopJ., CruikshankD.: Carboplatin and continuous infusion of 5-fluorouracil for advanced head and neck cancer.Eur. J. Cancer Clin. Oncol., 25: 173–176, 1989.
15.
PetoJ.: The calculation and interpretation of survival curves. In: Cancer Clinical Trials. Methods and Practice.BuyseM.E., StaquetM.J., SylvesterR.J. (Eds.), pp. 361–377. Oxford University Press, 1984.
16.
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.
17.
RozencweigM., DodionP., BruntschU., GallmeierW., ClavelM., GignouxB., Cortes-FunesH., CavalliF., KirkpatrickA., DalesioO., Van RijmenantM.: Combination chemotherapy with cisplatin, methotrexate, bleomycin and vincristine (CABO) in advanced squamous cell carcinoma of the head and neck.Cancer, 54: 1499–1503, 1984.
18.
SchullerD.E., WilsonH.E., SmithR.F., BatleyF., JamesA.D.: Preoperative reductive chemotherapy for locally advanced carcinoma of the oral cavity, oropharynx and hypopharynx.Cancer, 51: 15–19, 1983.
19.
SpauldingM., ZieglerP., SandquistN., KlotchD., LeeK., KhanA., LoreJ.: Induction therapy in head and neck cancer.A comparison of two regimens. Cancer, 57: 1110–1114, 1986.
20.
SridharK.S., OhnumaT., BillerH., HollandJ.F., AmbinderE.P., BarbaJ.: Combination chemotherapy with high-dose methotrexate, bleomycin and cisplatin in the management of head and neck squamous cell carcinoma.Am. J. Clin. Oncol., 8: 55–60, 1985.
VoglS.E., SchoenfeldD.A., KaplanB.H., LernerH.J., EngstromP.F., HortonJ.: A randomized prospective comparison of methotrexate with a combination of methotrexate, bleomycin and cisplatin in head and neck cancer.Cancer, 56: 432–442, 1985.
23.
VollingP., SchroderM., RauschningW., AchterrathW., StennertE.: Carboplatin.The better platinum in head and neck cancer. Arch. Otolaryngol. Head Neck Surg., 115: 695–698, 1989.
24.
WeichselbaumR.R., ClarkJ.R., MillerD., PosnerM.R., ErvinT.J.: Combined modality treatment of head and neck cancer with cisplatin, bleomycin, methotrexate-leucovorin chemotherapy.Cancer, 55: 2149–2155, 1985.
25.
WendtT.G., HartensteinR.C., WustrowT.P.V., LissnerJ.: Cisplatin, fluorouracil with leucovorin calcium enhancement and synchronous accelerated radiotherapy in the management of locally advanced head and neck cancer.A phase II study. J. Clin. Oncol., 7: 471–476, 1989.
26.
WilliamsS.D., Velez-GarciaE., EssesseeI., RatkinG., BirchR., EinhornL.H.: Chemotherapy for head and neck cancer.Comparison of cisplatin + vinblastine + bleomycin versus methotrexate. Cancer, 57: 18–23, 1987.
