Systemic therapy for gynaecological cancer — structured SAQ (15 marks)

(a) First-line regimen and trial (3 marks)

• Carboplatin (AUC 5-6) plus paclitaxel (175 mg/m2), every three weeks for six cycles. (2)
• Established by GOG-158 (Ozols 2003): carboplatin-paclitaxel equivalent to cisplatin-paclitaxel with less toxicity. (1) ^[2]

(b) Calvert calculation (3 marks)

• Formula: dose (mg) = target AUC × (GFR + 25). (1) ^[1]
• Working: 5 × (65 + 25) = 5 × 90. (1)
• Dose = 450 mg. (1)

(c) Maintenance (4 marks)

• BRCA1 mutation selects a PARP inhibitor (olaparib) as maintenance, by synthetic lethality — the tumour lacks homologous recombination and dies when PARP is blocked. (2) ^[7]
• SOLO-1 (5-year follow-up, Banerjee 2021): median PFS 56.0 months olaparib vs 13.8 months placebo, hazard ratio 0.33 (95% CI 0.25-0.43). (2) ^[5]

(d) Neutropenic sepsis (3 marks)

• Recognise as neutropenic sepsis until proven otherwise — nadir falls at 7-14 days post-cycle. (1) ^[8]
• Take cultures and give empirical broad-spectrum anti-pseudomonal antibiotics within one hour, without waiting for the full blood count. (1)
• Admit for observation and notify the oncology team. (1)

(e) Mechanisms and toxicities (2 marks)

• Cisplatin: forms DNA crosslinks blocking replication; signature toxicities nephrotoxicity, ototoxicity, neurotoxicity, emesis. (1)
• Paclitaxel: stabilises microtubules, arrests mitosis at G2/M; signature toxicities peripheral neuropathy, alopecia, infusion reaction. (1) ^[2]