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

FRANZCOG-format structured SAQ on gynaecological systemic therapy: the carboplatin-paclitaxel backbone and GOG-158, the Calvert AUC calculation, BRCA-selected PARP inhibitor maintenance (SOLO-1), the management of neutropenic sepsis, and platinum vs taxane mechanism. Per-sub-part marking rubric included.

Prompt

A 56-year-old woman undergoes optimal cytoreductive surgery for stage IIIC high-grade serous ovarian cancer; germline testing confirms a pathogenic BRCA1 variant. The oncology plan is carboplatin-paclitaxel for six cycles followed by maintenance therapy. (a) State the first-line chemotherapy regimen with drug, dose and schedule, and name the trial that established it. (3 marks) (b) Calculate the carboplatin dose for her first cycle using the Calvert formula, showing your working, for a measured GFR of 65 mL/min and a target AUC of 5. (3 marks) (c) Outline the rationale and the maintenance option best supported by her BRCA1 status, citing the pivotal trial and its key result. (4 marks) (d) Two weeks after cycle 3 she presents febrile (38.6°C) to her generalist. Detail your immediate management and the principle that governs it. (3 marks) (e) Contrast the mechanisms of cisplatin and paclitaxel, and name the signature toxicity of each. (2 marks)

How this SAQ is marked

Marks come from specifics: the named regimen with doses, the working of the Calvert calculation, the trial name and its hazard ratio, and the immediate action for neutropenic sepsis. Write in short labelled points. ^[2]

Reveal model answer and mark schemeShow

(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]

References5Show

[1]Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function J Clin Oncol, 1989.PMID 2681557
[2]Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study J Clin Oncol, 2003.PMID 12860964
[5]Banerjee S, Moore KN, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial Lancet Oncol, 2021.PMID 34715071
[7]Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers N Engl J Med, 2009.PMID 19553641
[8]Redondo A, Guerra E, Manso L, Martin-Lorente C SEOM clinical guideline in ovarian cancer (2020). Clin Transl Oncol, 2021.PMID 33515422