O&G · Gynae-oncology — systemic therapy
Systemic therapy for gynaecological cancer — what the generalist must know
Also known as Gynae-oncology chemotherapy · Carboplatin-paclitaxel · Platinum agents · Taxanes · PARP inhibitors · Pembrolizumab in gynaecological cancer
Exam-exhaustive FRANZCOG reference on systemic therapy in gynaecological malignancy written for the generalist who must understand (not prescribe) the oncologist's plan: the platinum agents with carboplatin dosing by the Calvert AUC formula, the taxanes, the carboplatin-paclitaxel first-line backbone for ovarian cancer, bevacizumab, PARP inhibitors and their synthetic-lethality mechanism, checkpoint immunotherapy, and the recognition and management of the common toxicities including neutropenic sepsis. RANZCOG-primary, globally tagged.
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Red flags
- A febrile patient within 7-14 days of chemotherapy is neutropenic sepsis until proven otherwise — cultures and empirical antibiotics within the hour, never wait for the FBC
- Paclitaxel infusion reactions cluster in the first two cycles (non-IgE, Cremophor vehicle); carboplatin hypersensitivity comes late, on rechallenge, and is IgE-mediated — the two are different emergencies
- A patient on a PARP inhibitor with falling blood counts may have myelosuppression or, rarely, secondary MDS/AML — persistent cytopenias demand a marrow exam
- Diarrhoea, breathlessness or an endocrine complaint in a patient on pembrolizumab is an immune-related adverse event until excluded, not a routine infection
- Carboplatin dosed by mg/m2 rather than the Calvert AUC formula risks dangerous under- or over-dosing — it is always dosed to renal function
- Cisplatin requires pre- and post-hydration, magnesium monitoring and antiemesis; casually substituting it for carboplatin without these safeguards causes renal and electrolyte harm
A woman leaves the gynaecological oncology MDT with a plan: "carbo-paclitaxel six cycles, then maintenance." She will spend more time with you, her generalist, during those cycles than with her oncologist. She will have nausea, numb fingers, a low temperature, and questions. This topic teaches you to read the oncologist's plan, dose the one drug that is renally calculated, recognise the toxicities by name and by day, and act on the single emergency — neutropenic sepsis — within the hour. [8]
You are not expected to run the chemotherapy regimen. You are expected to know what is being given, why, what it does to the patient in front of you, and when to pick up the phone. [8]
Overview and definition
Systemic therapy in gynaecological cancer falls into four drug families, and the generalist should hold them as four distinct tools: [8]
- Platinum agents (cisplatin, carboplatin): DNA crosslinkers
- Taxanes (paclitaxel, docetaxel): microtubule stabilisers
- Backbone of ovarian and advanced endometrial treatment
- Bevacizumab: anti-VEGF monoclonal antibody
- Front-line and recurrent ovarian; advanced cervical
- Hypertension, proteinuria, bleeding/bowel perforation
- Olaparib, niraparib, rucaparib, talazoparib
- Synthetic lethality in BRCA/HRD tumours
- Maintenance after platinum response
- Pembrolizumab (anti-PD-1 checkpoint)
- dMMR/MSI-H and PD-L1-high tumours
- Immune-related adverse events
The platinum-taxane combination is the spine of epithelial ovarian cancer treatment and of much advanced endometrial cancer. Cisplatin remains central to cervical cancer as concurrent chemoradiation. The targeted and immune agents extend the ladder upward, selected by molecular phenotype — and that phenotype is increasingly the hereditary status you met in the previous topic. [8]
References8ShowHide
- [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
- [3]Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer N Engl J Med, 2011.PMID 22204724
- [4]Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer N Engl J Med, 2016.PMID 27717299
- [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
- [6]Colombo N, Dubot C, Lorusso D, et al. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer N Engl J Med, 2021.PMID 34534429
- [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