Chemotherapy for Low-Grade Gliomas in Children

Treatment

Chemotherapy has been used for progressive residual or recurrent LGGs after an incomplete resection (<95% of the tumor resected). The most experience has been with optic pathway tumors. Those with neurofibromatosis or with the KIAA1549-BRAF fusion have better event-free and overall survival rates as compared to others managed with chemotherapy. Although most patients will not have a complete response, chemotherapy can be helpful for those with dissemination or unresectable lesions.

Carboplatin and vincristine (regimen A)

COG has reported on a protocol using carboplatin and vincristin to treat LLG in children (3).  Induction spans the first 12 weeks of chemotherapy and consists of the following:

• Days 1, 8, 15, 22, 43, 50, 57, 64: Carboplatin, 175 mg/m², as an IV infusion over 60 minutes
• Days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64: Vincristine, 1.5 mg/m² (0.05 mg/kg if child weighs <12 kg) (maximum dose, 2.0 mg) as an IV bolus infusion

Eight 6-week cycles of maintenance chemotherapy follow, consisting of the following:

• Days 1, 8, 15, 22: Carboplatin, 175 mg/m², as an IV infusion
• Days 1, 8, 15: Vincristine, 1.5 mg/m², as an IV infusion

Thioguanine, procarbazine, CCNU and vincristine (alternative regimen B)

Ater et al. also proposed an alternative regimen (3):

• Days 1–3: Thioguanine, 30 mg/m² PO every 6 hours for 12 doses
• Days 3, 4: Procarbazine, 50 mg/m² every 6 hours PO for 4 doses
• Day 4: CCNU (lomustine), 110 mg/m² PO Day 3
• Days 15 and 29: Vincristine, 1.5 mg/m² (0.05 mg/kg if child weighs < 12 kg) (2 mg maximum) IV

Vinblastine

Bouffet et al. proposed a treatment with vinblastine given over a 1-year span (5).

• Weekly: Vinblastine, 6 mg/m2, IV weekly for 52 weeks

Everolimus

Everolimus, 3 mg/m2/day PO is now FDA and Health Canada approved for progressive unresectable giant cell astrocytoma in tuberous sclerosis.

Other

Other regimens to consider in multiple recurrences include bevacizumab plus irinotecan (56); cisplatin plus etoposide 55.

Adjuvant Therapy

• Radiation: Usually reserved for older patients who have had at least one progression on chemotherapy. Always ensure that there has been no dissemination prior to radiation planning (21).

Complications

If significant complications occur during chemotherapy treatment of LGGs, the usual response is to manage the complication by modifying the dose of the chemotherapy. Supportive care may also be required.

• Pancytopenia: This is usually mild. It uncommonly results in a need for admission with fever and neutropenia.
• Neuropathy: This is usually mild to moderate, but the patient may need ankle/foot orthotics and physiotherapy to maintain range of motion.
• Ileus: This is uncommon when an appropriate bowel regimen is in place.
• Liver: A mild transaminitis usually is the only manifestation if there is any liver complication at all. Rarely, a chronic hepatopathy can occur.
• Stomatitis: This is mild if present.
• Hypersensitivity to carboplatin: This occurs in up to 20% of those treated with carboplatin, necessitating a change in regimen.

Outcome

Carboplatin and vincristine

• 5-year EFS rate: 39%

Thioguanine, procarbazine, CCNU, and vincristine

• 5-year EFS rate: 52%

Vinblastine

• 5-year PFS rate: 42%