Brain Tumors (Intracranial Carcinomas)                                                                                                  103

 

17. Brain Tumors (Intracranial Carcinomas)       

 

17.1        General considerations

Intracranial tumors are a heterogeneous group of malignancies each having its own biology, treatment and prognosis.

 

Histologic classification of selected tumors of the central nervous system* :

Tumors of neuroepithelial tissue

- Astrocytoma

- Anaplastic astrocytoma

- Glioblastoma multiforme

- Oligodendroglioma

- Anaplastic oligodendroglioma

- Oligoastrocytoma

- Anaplastic oligoastrocytoma

- Medulloblastoma

- Primitive neuroectodermal tumor

            Meningeal tumors

            Primary central nervous system lymphomas

            Germ cell tumors

            Tumors of the sellar region

Metastatic tumors

 

Cytoreductive surgery and radiotherapy are the standard initial procedures for highgrade astrocytic tumors ( WHO grade III: anaplastic astrocytoma, WHO grade IV: glioblastoma multiforme). Adjuvant chemotherapy post radiation may increase the percentage of long-term survivors but is of no or minor benefit for the majority of patients. For relapsed patients re-resection, stereotactic radiotherapy/ radiosurgery and/ or chemotherapy are therapeutic options for suitable patients.

 

Oligodendrogliomas (and mixed gliomas) are more sensitive to chemotherapy which can be given adjuvantly ( or neoadjuvantly) with radiotherapy or at the time of tumor progression.

 

Literature: for review e.g.

            BRANDES et al, Eur. J. Cancer 37 ( 2001): 2297 – 2301

            De ANGELIS, N. Engl. J. Med. 344 (2001): 114-123

            GALANIS and BUCKNER, Curr. Opin. Neurooncol. 13 (2000): 619 – 625 and

            Brit J Cancer 82 (2000): 1371 – 1380 (high-grade gliomas)

            GUTMAN et al, J. Control. Release 65 (2000): 31-41(targeted drug delivery)

            HOFER and HERRMANN, J. Cancer Res. Clin. Oncol. 127 (2001): 91-95

            (astrocytic and oligodendroglial tumors)

            HUNCHAREK et al, Anticancer Res. 18 (1998): 4693 – 4698 (meta-analysis of

            Monotherapy vs combination therapy)

            LAM and BREAKEFIELD, Hum. Mol. Genet. 10 (2001): 777- 787 (gene therapy)

104                                                                                                     Brain tumors (Intracranial Carcinomas)                                     

 

                        LESSER, Semin. Radiat. Oncol. 11 (2001): 138-144 (chemotherapy of lowgrade gliomas)

                        NEWTON, Expt. Opin. Investig. Drugs 9 (2000): 2815-2829 (new drugs)

PRADOS and LEVIN, Semin. Oncol. 27 (Suppl 6) (2000): 1 – 10 (biology and treatment of malignant gliomas)

                        TURINI and REDAELLI, Int. J. Clin. Pract. 55 (2001):471-475

 

17.2        Primary brain tumors

 

17.2.1 General recommendations

 

17.2.1.1Single agent chemotherapy

Treatment may be attempted with nitrosourea derivatives e.g.

BCNU                               200 mg/m2                           i.v.                             d 1 or

                                            80 mg/m2                           i.v.                             d 1 – 3

            To be repeated every 6 – 8 weeks

 

            Or

           

ACNU                                   100 mg/m2                       i.v. (1 – 3 min inf)       d 1

            To be repeated every 4 – 6 weeks

           

            Temozolomide

Temozolomide                        150 mg /m2*                     p.o.                            d 1 – 5 or

                                                 200 mg/m2                       p.o.                             d 1 – 5

            To be repeated every 4 weeks

            * Especially for patients pretreated with chemotherapy

            ** Especially for patients without prior chemotherapy

 

            Literature:

CHINOT et al, J. Clin. Oncol. 19 (2001): 2449 – 2455 (recurrent anaplastic oligodendrogliomas)

OSOBA et al, J. Clin. Oncol. 18 (2000): 1481-1491 (quality of life of patients with recurrent glioblastoma multiforme treated with either temozolomide or procarbazine)

YUNG et al, J. Clin. Oncol. 17 (1999): 2762 – 2771 (multicenter phase II study,  anaplastic astrocytoma or anaplastic oligoastrocytoma a first relapse)

 

The administration of vincristine, methotrexate, procarbazine, hydroxyurea, cisplatin, carboplatin, irinotecan, fotemustine, or teniposide may also be considered.

           

Interstitial chemotherapy with BCNU incorporated into biodegradable polymers (GliadelR) can be delivered directly to brain tumors at the time of surgery.

 

            Literature:

                        BREM et al, Lancet 345 (1995): 1008 – 1012

 

17.2.1.2 Combination chemotherapy

To date no multidrug treatment was proven to be superior to currently available single agent therapies.

 

Literature:

PRADOS et al, J. Clin. Oncol. 17 (1999): 3389-3395 (retrospective comparison of PCV and BCNU from the Radiation Therapy Oncology Group- RTOG-)

IV                                  any T                           any N                                        M 1

 

Anal carcinoma can develop in the mucosa-lined anal canal or the more distal epidermis-covered anal margin. The latter are considered skin cancers and are treated with local excision.

 

Radio-chemotherapy has become the primary treatment of choice for locally advanced stages > 1 carcinoma of the anal canal. Surgery is regarded as a rescue treatment for partial responders or in relapsing. Palliative chemotherapy (often 5-FU/platin-based) can be tried in cases with primary metastases or metachronous multiple metastases.

 

Literature: for review e.g.

            RYAN et al, N. Engl. J. Med. 324 (2000): 792 – 800

            SPRATT, J. Surg. Oncol. 74 (2000): 160 – 170

WHITEFORD et al, Arch. Surg. 136 (2001): 886 – 891 (retrospective consecutive case review)

 

105

            PCV

CCNU                                 110 or 130 mg/m2              p.o.                              d 1

Procarbazine                         60 or 75 mg/m2 *             p.o.                              d 8 – 21

Vincristine                            1.4 mg/m2                         i.v.                               d 8 + 29

                                              (max 2.0 mg)

            To be repeated every 6-8 weeks

 

            Literature:

                        LEVIN et al, Int. J. Radiat. Oncol. Biol, Phys, 18 (1990): 321 – 324

                        * CAIRNCROSS et al, J. Clin. Oncol. 12 (1994): 2013 – 2021

 

                        or

Procarbazine                           100 mg/m2                     p.o.                                   d 1 – 10

CCNU                                     100 mg/m2                     p.o.                                   d 1

Vincristine                               1.5 mg/m2                     i.v.                                    d 1

                                               (max 2 mg)

            To be repeated every 6 weeks (max 12 courses)

 

            Literature:

MEDICAL RESEARCH COUNCIL BRAIN TUMOUR WORKING PARTY, J. Clin. Oncol. 19 (2001): 509- 518 (no benefit of adjuvant PCV, when added to radiotherapy, was found in a randomized study)

 

            ICE (salvage therapy for recurrent malignant gliomas)

Ifosfamide                                750 – 1200 mg/m2*         i.v.                               d 1 – 3

                                                                                          With mesna uroprotection

Carboplatin                              75 mg/m2                        i.v.                                 d 1 – 3

Etoposide                                 75 mg/m2                        i.v.                                 d 1 – 3

            To be repeated every 4 weeks

            * According to hematological tolerance

           

            Literature:

                        SANSON et al, Eur. J. Cancer 32 A (1996): 2229 – 2235

 

17.2.2 High grade astrocytic tumors, glioblastoma

Anaplastic astrocytomas are more chemosensitive than glioblastomas: in low-grade astrocytic tumors: at present no generally agreed role of chemotherapy.

Single agent chemotherapy               see 17.2.1.1

PCV                                                   see 17.2.1.2

 

17.2.3 Ependymal tumors

In a retrospective analysis from the Memorial Sloan- Kettering Cancer Center, chemotherapy, specifically Carboplatin,was found to be able to give prolonged progression- free survival in some patients.

 

Literature:

            BERGEMANN and De ANGELIS, Proc. ASCO 20 (2001): 65; abstr. 258

 

17.2.4 Oligodendroglial tumors

Literature: for review

            PALEOLOGOS and CAIRNCROSS, Neuro-oncol. 1 (1999): 52 – 60

 

Single agent chemotherapy                 see 17.2.1.1

PCV                                                     see 17.2.1.1

106                                                                                                     Brain tumors (Intracranial Carcinomas)                                     

 

17.2.5 Pediatric malignant brain tumors

Literature: for review e.g.

            CHASTAGNER et al, Eur. J. Cancer 37 (2001): 1981- 1993

FREEMAN and PERILONGO, Child’s Nerv Syst. 15 (1999): 545-553 (brain stem gliomas) SCHMANDT and PACKER, Curr. Opin. Oncol. 12 (2000): 199-204 (treatment of low-grade pediatric gliomas)

 

           

8-drugs-in-one-day-regime ( “8 in1”)

Drug                                                  Regimen A                                      Regimen B

                                                           (mg/m2)                                            (mg/m2)
Methylprednisolone                           300                                                    300
Vincristine                                         1.5 (max 2.0)                                      1.5 (max 2.0)
CCNU                                                75                                                       75
Procarbazine                                       75                                                       75
Hydroxyurea                                       1500                                                   3000
Cisplatin                                              60                                                       90
Cytarabine                                           300                                                     300
Cyclophosphamide                              300                                                         -
Dacarbazin                                             -                                                       150

To be repeated every 2 – 4 weeks (as long as tolerated or until progression)

Regimen A : Medulloblastoma, PNET, ependymoma                 Regimen B: glioblastoma

 

Literature:

            GEYER et al, J. Clin. Oncol. 12 (1994): 1607-1615

            PENDERGRASS et al. J. Clin. Oncol. 5 (1987): 1221 – 1231

 

ICE

Ifosfamide                                           2000 mg/m2        i.v.                             d 1-3

                                                                                        With mesna uroprotection

Carboplatin                                          400 mg/m2          i.v.                             d 1

Etoposide                                              100 mg/m2         i.v.                             d 1-3

To be repeated every 3 weeks

 

Literature:

LOPEZ-AGUILAR et al, Arch. Med. Res. 31 (2000): 186-190 (Postoperative treatment of anaplastic astrocytomas and glioblastoma multiforme)

 

Or

 

Ifosfamide                                          1800 mg/m2         i.v.                                d 1 – 5

                                                                                       With mesna uroprotection

Carboplatin                                          400 mg/m2          i.v.                             d 1 + 2

Etoposide                                              100 mg/m2         i.v.                             d 1- 5

To be repeated every 3 weeks (with G-CSF support)

 

Literature:

            SHEN et al, Proc. Ann. Meet. Am. Soc. Clin. Oncol. 18 (1999): 558, abstr. 2151

            (salvage therapy for recurrent/refractory CNS malignancies )

 

 

 

Brain Tumors (Intracranial Carcinomas)                                                                                                  107

 

17.3    Tumors of embryonal origin (medulloblastoma)

Literature: for review e.g.

            BRANDES et al, Cancer Treat. Rev. 25 (1999): 3-12 (adult patients)

            CHINTAGUMPALA et al, Curr. Opin. Oncol. 13 (2001): 148 – 153

 

17.3.1.                       VCP

Vincristine                                     1.5 mg/m2                  i.v.                           d 1, 8, 15

CCNU                                            100 mg/m2                 p.o.                          d 1

Prednisone                                      40 mg/m2                  p.o.                          d 1 – 14

To be repeated every 6 weeks (in study CCG-921 eight courses preceded by an “ induction” period of eight weekly vincristine 1.5 mg/m2 injections during radiotherapy)

 

Literature:

            ZELTZER et al, J. Clin. Oncol. 17 (1999): 832-845

 

17.3.2 8-drugs-in-one-day-regime (“8 in 1”)

see 17.2.5

 

17.3.3.                        ICE

See 17.2.5

 

17.4        Tumors of mesenchymal origin

Doxorubicin containing regimes, see 45.2.1 and 45.2.2

 

17.5        Primary lymphomas of the CNS

For details please see indication 13, in particular chapter 13.4 “ Primary central nervous system NHL (PCNSL) “.

 

17.6        Primary germ cell tumors of the CNS

Pure germinoma tumors can be treated successfully with radiotherapy. In case of recurrence, patients can be rescued with both radiotherapy and chemotherapy.

 

Non-germinomatous germ cell tumors are highly chemosensitive and are treated with cisplatin-based induction chemotherapy (see 25.2.2) followed by consolidation radiotherapy.

 

Literature: for review e.g.

            BRANDES et al, Cancer Treat. Rev. 26 (2000): 233- 242

            PACKER et al, Oncologist 5 (2000): 312-320

 

17.7        Brain metastases

Cerebral metastases of tumors sensitive to chemotherapy may be treated with a regimen that is also effective against the extracranial disease.

 

Literature:

BOOGERD et al, Cancer 69 (1992): 972-980 (CMF or CAF for brain metastases form breast cancer) and J. Neurooncol. 41 (1999): 285-289 (teniposide for brain metastases from NSCLC)

            CAPPUZZO et al, Forum 10 (2000): 137 – 148 (review)

FRANCIOSI et al, Cancer 85 (1999): 1599-1605 (cisplatin + etoposide for brain metastases from breast cancer, NSCLC and melanoma)

            KRISTENSEN et al, J. Clin. Oncol. 10 (1992): 1498 – 1502 (brain metastases from SCLC)