Table 1.

Mode of Administration and Laboratory Values Required to Allow Treatment Initiation (Expert Opinion)

	Dosing	Mode of Administration	Preconditions for Drug Administration						Prophylaxis	Controls
			Neutrophils	Lymphocytes	Platelets	Hemoglobin	Liver Enzymes	Others
Temozolomide	75 mg/m2 during radiotherapy 7 days a week 150–200 mg/m2 (days 1–5 out of 28 days) as a single agent; Minimal dose during maintenance: 100 mg/m2	Oral, i.v. application no longer available Capsules should be swallowed whole with approximately 250 mL (1 glass) of water while fasting, in the morning, ie, at least 1 h before a meal or 2 h after a meal Concomitant with RT, capsules should be taken approximately 1 h before administration of RT	≥1.5 × 109/L	—	≥100 × 109/L	—	Normal liver function	Nonhematological toxicity CTCAE grade ≤1, except for alopecia, nausea, and vomiting	Antiemetic prophylaxis Concomitant: 5-HT3 antagonists usually only required for the initial 2–3 doses of temozolomide. Then simple antiemetic prophylactic treatment with metoclopramide or domperidone is sufficient for most patients, some patients may not require any antiemetic Maintenance: Strongly recommended prophylaxis: 5-HT3 antagonist, low dose, eg, ondansetron 4 mg or granisetron 1 mg p.o. 1 h prior to temozolomide administration Pneumocystis jirovecii prophylaxis Concomitant: Per label required for all patients regardless of lymphocyte count during RT and beyond until any lymphopenia has recovered to CTCAE grade ≤1, but debatable for patients without corticosteroids and without lymphopenia Maintenance: all patients if lymphocytes ≤0.8 × 109/L (CTCAE grade ≥1) or CD4 count ≤ 200/μL, particularly patients receiving steroids should be observed closely for the development of pneumocystis jirovecii pneumonia Proposed prophylaxis Pentamidine inhalations by nebulizer once a month or trimethoprim–sulfamethoxazole (Bactrim forte) 1 tablet/3× per week	During concomitant radiochemotherapy: weekly complete blood count and liver enzymes During maintenance: complete blood count (days 21 and 28) and, liver enzymes at day 21
Procarbazine	100–150 mg daily, in the PCV protocol 60 mg/m2 on days 8 through 21	Oral	≥1.5 × 109/L	—	≥100 × 109/L	—	—	Nonhematological toxicity grade ≤1, except for alopecia, nausea, and vomiting	5-HT3 antagonist, low dose, eg, ondansetron 4 mg or granisetron 1–2 mg p.o. 1 h prior to administration
Lomustine	130 mg/m2 single agent, 110 mg/m2, in the PCV protocol or in combination with bevacizumab, commonly capped at 200 mg, ×6–8 weeks	Oral	≥1.5 × 109/L	—	≥100 × 109/L	—	—	Nonhematological toxicity grade ≤1, except for alopecia, nausea and vomiting Pulmonary examination and nerve conduction studies prior to first cycle not routinely, but only with appropriate history	Recommended prophylaxis: 5-HT3 antagonist or metoclopramide p.o. 1 h prior to lomustine administration	At days 28 and 35 complete blood counts, at day 42 complete blood count and blood chemistry
Vincristine	2 mg, days 8 and 29 in the PCV protocol	i.v.	≥1.5 × 109/L	—	≥100 × 109/L	—	—	Discontinuation for any clinical signs of peripheral neuropathy		Complete blood count, vincristine alone is only weakly myelosuppressive, but commonly given together with other other myelosuppressive agents
PCV		Oral and i.v.	≥1.5 × 109/L	—	≥100 × 109/L	—	—	See lomustine, procarbazine, and vincristine Pulmonary examination and nerve conduction studies prior to first cycle not routinely, but only with appropriate history	Recommended prophylaxis: 5-HT3 antagonist or metoclopramide p.o. 1 h prior to lomustine administration, 5-HT3 antagonist on day 1 and 2 p.o. 1 h prior procarbazine and metoclopramide as needed during procarbazine administration	At days 8 and 29 complete blood counts, after week 6 complete blood count and blood chemistry
Bevacizumab	10 mg/kg × 14 days or 15 mg/kg × 3 weeks i.v.	i.v.	≥1.5 × 109/L	—	≥100 × 109/L	—	—	Liver function: CTCAE grade 1 allowed Microproteinuria allowed	—	Complete blood count and liver enzymes every 14 days and additional urine status 48 h before next infusion cycles Weekly or even shorter controls might be necessary depending on laboratory values Blood pressure prior/during and after infusion Careful assessment for any clinical signs of deep vein thrombosis Educate patients to report immediately any signs of shortness of breath (pulmonary embolism or myocardial infarction) or abdominal pain
Vemurafenib	960 mg twice daily	Oral Avoid concomitant administration with strong CYP3A4 inhibitors or inducers	≥1.5 × 109/L	—	≥75 × 109/L	—	—	ECG (QT time) Dermatological examination prior to drug initiation	Avoid sun exposure, use of sunscreen, not to be used during RT	Every 4 weeks blood counts and blood chemistry including electrolytes, First 3 months monthly ECG (QT time), thereafter every 3 months Dermatological examination every 3 months
Dabrafenib/tramatenib	Dabrafenib 2 mg daily, trametinib 150 mg twice daily	Oral Take dabrafenib and trametinib with water at least 1 hour before or 2 hours after a meal Avoid concurrent administration of strong inhibitors of CYP3A4 or CYP2C8	≥1.5 × 109/L	—	≥75 × 109/L			Cardiac function: ECG, left ventricular ejection fraction Dermatological examination prior to drug initiation	Avoid sun exposure, use of sunscreen, not to be used during RT	Every 4 weeks blood counts and blood chemistry including electrolytes Monthly control of blood pressure Every 3 months left ventricular ejection fraction Dermatological examination every 3 months
Laroctrectinib and entrectinib	Larotrectinib: 100 mg twice daily; minimal dose: 50 mg twice daily Symptoms of overdose are not established. In the event of overdose, physicians should follow general supportive measures and treat symptomatically Entrectinib: 600 mg once daily; minimal dose: 200 mg once daily	Larotrectinib Oral (capsule or oral solution); capsules or oral solution should be swallowed whole with approximately 250 mL (1 glass) of water with or without food but should not be taken with grapefruit or grapefruit juice Entrectinib Capsules or oral solution should be swallowed whole with approximately 250 mL (1 glass) of water with or without food but should not be taken with grapefruit or grapefruit juice	CTCAE grade 1 and 2 allowed	≥1 × 109	≥100 × 109/L	CTCAE grade 1 and 2 allowed	Normal liver function	—	No specific prophylaxis Potential interaction with other medications (such as anti-HIV drugs, sartans, statins, antidiabetics, warfarin) to be considered Women using systemically acting hormonal contraceptives should be advised to add a barrier method	Liver function: before the first dose and monthly for the first 3 months of treatment, then periodically during treatment, with more frequent testing in patients who develop transaminase elevations Patients with grade 2 ALT and/or AST increases should be followed with serial laboratory evaluations every 1 to 2 weeks

ALT, alanine transaminase; AST, aspartate aminotransferase; CTCAE, Common Terminology Criteria for Adverse Events; ECG, electrocardiogram; HIV, human immunodeficiency virus; i.v., intravenous; p.o., per os; RT, radiotherapy.