Single Agent Carboplatin in Early Ovarian Cancer
Single-agent carboplatin for 6 cycles is an acceptable and evidence-based treatment option for adjuvant chemotherapy in early-stage ovarian cancer requiring treatment, with Level I evidence supporting its use. 1
Who Should Receive Adjuvant Chemotherapy
Adjuvant chemotherapy should be offered to patients with early-stage ovarian cancer (stage I–IIA) except for fully staged patients with: 1
- Low-grade serous stage IA
- Grade 1 and 2 endometrioid stage IA
- Grade 1 and 2 mucinous stage IA (expansile invasion)
High-risk patients requiring treatment include: 1
- Stage IC (all grades)
- Stage IB or IC grades 2 and 3
- Clear cell histology
- Stage IIA disease
The benefit of adjuvant chemotherapy is uncertain for clear cell carcinoma stage IA/IB/IC1, grade 1-2 endometrioid IB/IC, low-grade serous IB/IC, and should be discussed individually. 1
Treatment Regimen Options
For patients requiring adjuvant chemotherapy, acceptable regimens are: 1
- Carboplatin alone (Level I evidence, Strength A)
- Carboplatin/paclitaxel (Level II evidence, Strength A)
The 2019 ESMO-ESGO consensus achieved 100% agreement that both single-agent carboplatin and carboplatin/paclitaxel are acceptable options. 1
Duration of Treatment
For single-agent carboplatin: 6 cycles are recommended (Level I evidence, Strength A). 1
For carboplatin/paclitaxel: A minimum of 3 cycles is recommended, except for high-grade serous subgroup or stage IC (any histological type), for whom 6 cycles are recommended. 1
The GOG 157 trial demonstrated that 6 cycles of carboplatin/paclitaxel were not associated with longer progression-free or overall survival compared to 3 cycles, but were associated with significantly greater toxicity. 1 This supports the use of shorter duration for combination therapy in selected patients.
Evidence Supporting Single-Agent Carboplatin
Meta-analysis of 5 large prospective trials showed that platinum-based adjuvant chemotherapy improved overall survival (HR 0.71; 95% CI 0.53–0.93) and progression-free survival (HR 0.67; 95% CI 0.53–0.84) compared to observation. 1
The majority of patients in the ACTION/ICON1 trials (approximately 60%) received carboplatin monotherapy, and only 6% received taxanes, yet demonstrated survival benefit. 1 The ICON3 trial showed no benefit for adding paclitaxel to carboplatin in the 20% of patients with stage I-II disease. 1
Critical Caveat: Vulnerable Older Patients
Single-agent carboplatin should NOT be used in vulnerable older patients with advanced disease. The EWOC-1 trial (2021) was terminated early because single-agent carboplatin was associated with significantly worse survival compared to carboplatin-paclitaxel combinations in vulnerable older women (mean age 80 years) with stage III/IV disease. 2 However, this applies to advanced disease, not early-stage disease where single-agent carboplatin remains appropriate.
Practical Dosing
Carboplatin dosing: AUC 5-6 every 3 weeks for 6 cycles. 1, 3
For patients with impaired renal function (creatinine clearance <60 mL/min), dose adjustments are required: 3
- CrCl 41-59 mL/min: 250 mg/m²
- CrCl 16-40 mL/min: 200 mg/m²
Aluminum-containing needles or IV sets must not be used as aluminum reacts with carboplatin causing precipitate formation and loss of potency. 3
Toxicity Monitoring
Dose-limiting toxicity is thrombocytopenia. 3, 4 Treatment should not be repeated until neutrophil count ≥2,000 and platelet count ≥100,000. 3
Dose adjustments for subsequent cycles: 3
- Platelets >100,000 and neutrophils >2,000: increase to 125% of prior dose
- Platelets 50-100,000 or neutrophils 500-2,000: no adjustment
- Platelets <50,000 or neutrophils <500: reduce to 75% of prior dose
Single-agent carboplatin contributes minimally to cumulative sensory neuropathy compared to paclitaxel-containing regimens, ensuring better tolerability. 4