Opportunities in optimizing cytotoxic treatment of lung cancer in the era of immunotherapy

Based on the findings of this thesis, a series of evidence-based recommendations are proposed to optimize and personalize the dosing of carboplatin, pemetrexed, docetaxel, and atezolizumab in the treatment of advanced non-small cell lung cancer (NSCLC) patients..

For carboplatin, it is recommended to adopt cystatin C-based estimation of drug clearance. This approach incorporates patient-specific parameters including age, sex, body weight, and serum creatinine, and has shown superior accuracy and precision compared to traditional creatinine-based formulas like the Cockcroft-Gault formula in multiple prospective studies.

For pemetrexed, standard dosing poses a high risk of toxicity in patients with impaired renal function (GFR <45 mL/min). It is advised that new treatment regimens be developed for this subgroup, alongside the incorporation of prophylactic folinic acid supplementation (45 mg, four times daily on days 2–15 of a 21-day cycle), modeled after established methotrexate protocols, to mitigate possible adverse effects.

Regarding docetaxel, it remains a viable treatment option for advanced NSCLC patients previously treated with immunotherapy. However, hematological toxicity should not currently be used as a prognostic marker for survival outcomes. Further prospective research is required to clarify this potential association in the post-immunotherapy setting.

For atezolizumab, personalized dosing intervals based on patient weight are recommended: 5 weeks for <50 kg, 4 weeks for 50–65 kg, and the standard 3 weeks for >65 kg. This strategy allows immediate clinical implementation and yields notable dose reductions up to 12% in European and 11.7% in U.S. populations, while retaining effective therapeutic exposure.