Head and Neck Carcinoma                                                                                                                            159

 

28.     Head and Neck Carcinoma

 

28.1        General considerations

The majority of head and neck carcinomas in the “ Western World “ and of squamous cell histology, whereas undifferentiated carcinomas and lymphoepitheliomas/ anaplastic cancers of the nasopharynx predominate in Asia and the Middle East ( and among native American Eskimos).

 

Staging of  head and neck cancer is complicated by different criteria for each anatomic region (lip, oral cavity, and oropharynx/ hypopharynx/ nasopharynx/ larynx/maxillary sinus).

 

The American joint Commission on Cancer (AJCC) and the Union Internationale Contre Cancer (UICC) have a common staging system.

 

Stage grouping

Stage 0                    Tis                             N0                                M0

Stage 1                    T1                              N0                                M0

Stage II                   T2                              N0                                M0

Stage III                  T3                              N0                                M0

                                T 1 – 3                       N1                                M0

Stage IV                  T4                              N0 – 1                          M0

                                T0 – 4                        N2 – 3                          M0

                                T0 – 4                        N0 – 3                          M1         

Historically, surgery and/or radiotherapy were the mainstay of treatment of early (stage I and II) as well as locoregionally advanced squamous cell head and neck cancer. Chemotherapy was reserved for palliative treatment of patients with locally recurrent or refractory disease which often is not amenable for repeated resurgery or radiotherapy and for those with metastatic disease.

 

With the development of combined modality strategies, chemotherapy was integrated earlier in the treatment. When chemotherapy is added to the locoregional treatment (especially alternating or concomitant with radiotherapy) in patients with non-metastatic disease it may allow organ-preservation and add some benefit on survival (but also a burden on toxicity). Neither adjuvant nor neoadjuvant chemotherapy (not immediately followed by radiation therapy) produce significant benefits to date, and have to be considered investigational.

 

Nasopharyngeal cancer usually manifest at a more advanced stage but are also more chemotherapy-responsive than are other head and neck cancers. In earlydisease (stage I and II) radiotherapy is the treatment of choice. Patients with previously untreated locally advanced stage III and IV disease show improved local control, decreased systemic metastasis and improved disease-free and overall survival when treated with combination chemotherapy in conjunction with radiotherapy (sometimes followed by adjuvant chemotherapy).

 

Literature: for review e.g.

AGARWALA, Hematol, Oncol. Clin. North Am. 13 (1999): 743 – 752 (adjuvant chemotherapy)

CLAYMAN and DREILING, Hematol. Oncol. Clin. North Am. 13 (1999): 787 – 810 (direct injection of therapeutic agents into the tumor).

            FORASTIERE et al, N. Engl. J. Med. 345 (2001): 1890 – 1990

 

 

160                                                                                                                            Head and Neck Carcinoma

 

                        GANLY and KAYE, Ann. Oncol. 11 (2000): 11 – 16 (recurrent disease)

KHATTAB and URBA, Hematol. Oncol. Clin. North Am. 13 (1999): 752 – 768 (new agents)

                        MELLOT and VOKES, Cancer Treat, Res. 106 (2001): 221 – 235  

                        (chemoprevention)

PIGNON et al. Lancet 355  (2000): 949 – 955 (meta- analyses on chemotherapy added to locoregional treatment)

POSNER et al, Semin. Oncol. 27 (Suppl 8) (2000) : 13 – 24 (role of induction chemotherapy)

RUDAT and WANNENMACHER, Semin. Surg. Oncol. 20 (2001): 66 – 74 (role of multimodal treatment in oropharynx, larynx and hypopharynx cancer)

VOKES et al, Semin. Oncol. 27 (Suppl 8) ( 2000 ) : 34 – 38 ( concurrent radiochemotherapy for locoregionally advanced disease)

 

28.2        Squamous cell carcinoma

 

28.2.1 Single agent chemotherapy

Methotrexate              40 – 60 mg/m2               i.v. (short inf)                once weekly

 

Litrature:

            DeCONTI and SCHOENFELD, Cancer 48 (1981): 1061 – 1072

            VOGL et al, Cancer 56 (1985) : 432 – 442

 

Treatment may also be attempted with ciplatin, carboplatin, 5- fluorouracil, bleomycin , taxanes (decetaxel, paclitaxel), or ifosfamide.

 

28.2.2 Combination chemotherapy

 

28.2.2.1  Cisplatin + 5 – fluorouracil (numerous variations, e.g.)

Cisplatin                        100 mg/m2               i.v. (1 h inf)                  d 1

5 – Fluorouracil             1000mg/m2              i.v.( cont inf)                d  1- 4 (5)

            To be repeated every 3 – 4 weeks (also followed by radiotherapy)*

 

            Literature:

                        AL SARRAF, Semin. Oncol. 15 (1988) : 70 – 85

                     * DECKER et al, Cancer 51 (1983): 1353 – 1355

LEFEBVRE et al, J. Natl. Cancer inst. 88 (1996) : 890 – 899

O’BRIEN et al, Eur. J. Cancer 30B (1994): 265 – 267

PACCAGNELLA et al, J. Natl. Cancer Inst. 86 (1994): 265 – 272

ROONEY et al, Cancer 55 (1985): 1123 – 1128

ROWLAND et al, Cancer Treat, Rep. 70 (1986) : 461 – 464

 

28.2.2.2  Cisplatin + 5-fluorouracil + concomitant radiotherapy

Cisplatin                        20 mg/m2                 i.v. (30 min inf)                     d 1 – 5

5 – Fluorouracil             200 mg/m2               i.v. (cont inf)                         d 1 – 5

            With radiotherapy d 15 – 28. To be repeated d 29 (3 cycles).

 

            Literature :

                        MERLANO et al, Cancer 67 (1991): 915 – 921

 

 

Head and Neck Carcinoma                                                                                                                            161

 

28.2.2.3  Carboplatin + 5-fluorouracil

Carboplatin                        300 mg/m2                  i.v. (short inf)                  d 1

5-Fluorouracil                    1000 mg/m2                i.v. (cont inf)                   d 1 – 4

            To be repeated every 3 – 4 weeks

           

             Literature:

                        FORASTIERE et al, J. Clin. Oncol. 10 (1994): 1245 – 1251

 

28.2.2.4  Carboplatin + 5fluorouracil + concomitant radiotherapy

Carboplatin                         70 mg /m2                i.v. (bolus)                     d 1 – 4

5-Fluorouracil                    600 mg/m2                i.v. (cont inf)                 d 1 – 4

            To be repeated every 3 weeks ( 3 cycles  starting d 1,22, and 43). Radiotherapy:

            Total dose 70 Gy (2 Gy  per fraction, 5 fractions per week) delivered to be the 

             primary tumor and the involved lymph nodes.

           

            Literature:

                        CALAIS et al, J. Natl. Cancer Inst. 91 (1999): 2081 – 2086 (randomized   

                        trial of radiation vs concomitant chemoradiotherapy for stage III– IV 

                        oropharynx carcinoma)

 

28.2.2.5  IP

Ifosfamide                       1500 mg/m2                 i.v. (30 min inf)              d 1 – 5

                                                                            With mesna uroprotection

Cisplatin                          10 mg/m2                     i.v. (30 min inf)              d 1 – 5

            To be repeated every 4 weeks

           

            Literature:

                        PAI et al, Oncology 50 (1993): 86 – 91

 

28.2.2.6  TIP

Paclitaxel                          175 mg/m2               i.v. (3 h inf)                         d 1

Ifosfamide                        1000 mg/m2              i.v. (2 h inf)                        d 1 – 3

                                                                          With mesna uroprotection

Cisplatin                           60 mg/m2                  i.v.                                       d 1

            To be repeated every 3 – 4 weeks

 

            Literature:

                        SHIN et al, J.  Clin. Oncol. 16 (1998): 1325 – 1330

 

28.2.2.7  TIC

Paclitaxel                    175 mg/m2                  i.v. (3 h inf)                        d 1

Ifosfamide                   1000 mg/m2               i.v. (2 h inf)                        d 1 – 3

                                                                      With mesna uroprotection

Carboplatin                 AUC = 6                      i.v. (30 min inf)                 d 1

              To be repeated every 3 – 4 weeks

 

               Literature:     

                        SHIN et al, Cancer 91 (2001): 1316 – 1323

 

 

162                                                                                                                            Head and Neck Carcinoma

 

28.2.2.8  Docetaxel + cisplatin

Docetaxel                             100 mg./m2                  i.v. ( 1 h inf)                    d 1

Cisplatin                               75  mg/m2                             i.v. (3 h inf)                     d 1

          To be repeated every 3 weeks

 

Literature:

SCHOFFSKI et al, Ann. Oncol. 10 (1999): 119 – 122 (multicenter phase II trial of the EORTC Early Clinical Studies Group)

 

28.2.2.9  Docetaxel + cisplatin + 5 – fluorouracil (TPF)

Docetaxel                             75 mg./m2                    i.v.                                 d 1

Cisplatin                              100  mg/m2                             i.v.                                d 1

5-Fluorouracil                      1000 mg/m2                  i.v. (cont inf)                d 1-4

To be repeated every 3 weeks (3 cycles)

 

Literature: e.g.

            POSNER et al, J. Clin. Oncol. 19 (2001): 1096 – 1104

 

28.3                Nasopharyngeal carcinoma

Literature: for review e.g.

        ALI and AL SARRAF, Oncology 14 (2000): 1223 – 1230 , 1232- 1237,  

        1239-1242

        CHAN et al, Cancer 82 (1998): 1003 – 1012

 

28.3.1             Cisplatin + 5-fluorouracil + radiotherapy

Cisplatin                     100  mg/m2                         i.v. (1 h inf)                   d 1, 22,43

          With radiotherapy ( up to 70 Gy in 35 – 39 fractions) followed by

Cisplatin                     80  mg/m2                             i.v. (2 h inf)                  d 71, 99,127

5-Fluorouracil             1000 mg/m2                i.v. (cont inf)                d 71-74, 99-

                                                                                                           102,  127 – 130

 

            Literature:

                        AL SARRAF et al, J. Clin. Oncol. 16 (1998) ; 1310-1317 (randomized    

                        phase III Intergroup study 0099 of chemoradiotherapy vs radiotherapy)

 

28.3.2.         PBF

Cisplatin                     100  mg/m2                    i.v. (1 h inf)                   d 1

Bleomycin                  15 mg                       i.v. (bolus)                    d 1 followed by

                                   16 mg/m2                  i.v. (cont inf)                d 1 – 5

5-Fluorouracil             650 mg/m2               i.v. (cont inf)                d 1 - 5                     

          To be repeated every 4 weeks (2 cycles)

 

            Literature:

                        BOUSSEN et al, J. Clin. Oncol. 9 (1991): 1675 – 1681

 

 

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28.3.3.         BEC

Cisplatin                    100  mg/m2                   i.v. (1 h inf)                    d 1

Epirubicin                  70 mg/m2                i.v. (bolus)                     d 1

Bleomycin                 15 mg                      i.v. (bolus)                     d 1 followed by

                                  12 mg/m2                 i.v. (cont inf)                 d 1-5

          To be repeated every 4 weeks (neoadjuvant 2 – 3 courses)

 

           Literature:

            BACHOUCHI et al, J. Natl. Cancer Inst. 82 (1999): 616 – 620

 

28.3.4       IFL ( as second-line therapy)

Ifosfamide                      1200 mg/m2 *           i.v. (4 th inf)                   d 1 – 5

                                                                         With mesna uroprotection

Folinic acid                     20 mg/m2                 i.v. (bolus)                      d 1 – 5

5- Fluorouracil                375 mg/m2 **          i.v. (20 h inf)                   d 1 – 5

            To be repeated every 3 weeks (max 6 cycles)

*    Escalated to 1400 and to 1600 mg/m2 in subsequent cycles according to bone 

      marrow toxicity.

**  Escalated to 450 and to 525 mg/m2 in subsequent cycles according to the  

      severity of mucositis.

 

            Literature :

                        CHUA et al, Eur. J. Cancer 36 (2000): 736 – 741