For the treatment of recurrent glioblastoma, there are several systemic therapy options available, including rechallenge with temozolomide. The following table outlines some of the second-line therapies with their respective dosages, cycles, and potential toxicities:

Therapy	Dosage	Cycles	Toxicities
Temozolomide Rechallenge	150-200 mg/m² daily on days 1-5	Every 28 days, up to 6 cycles	Myelosuppression, nausea, vomiting, fatigue
Dose-Dense Temozolomide	100-150 mg/m² daily on days 1-7 and 15-21	28-day cycles, up to 12 cycles	Increased myelosuppression compared to standard dosing, fatigue, nausea
Bevacizumab	10 mg/kg every 2 weeks	Until progression or toxicity	Hypertension, proteinuria, thromboembolic events, gastrointestinal perforation

Additional Considerations

• Temozolomide Rechallenge: This approach is used if the patient initially responded to temozolomide. It is generally well-tolerated but requires monitoring for hematologic toxicities.
• Dose-Dense Temozolomide: This regimen aims to overcome resistance mechanisms and may offer benefits in some patients, though it is associated with higher toxicity.
• Bevacizumab: Approved for recurrent glioblastoma, it can help reduce edema and improve symptoms, but does not significantly extend overall survival.

Citations:

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487236/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10495891/

[3] https://ascopubs.org/doi/10.1200/JCO.2009.26.5520

[4] https://academic.oup.com/neuro-oncology/article/15/1/4/1373604

[5] https://www.mdpi.com/1718-7729/30/2/147

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3337418/

[7] https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.23813