BACKGROUND: Adjuvant carboplatin reduces relapse risk in clinical stage 1 (CS1) seminoma, though there is a paucity of long-term safety data. AIM: Our objective was to report long-term outcomes of two cycles of adjuvant carboplatin dosed at area under the time-concentration curve (AUC) of 7. METHODS AND RESULTS: We performed a retrospective analysis on treatment and outcomes of patients with CS1 seminoma who received adjuvant carboplatin from 2000 to 2016 at our centres in the Midland Region, New Zealand. Of 159 patients, median age 39 years, 153 received two cycles of carboplatin: 147 dosed at AUC7 and 6 at AUC6. Six patients had one cycle of carboplatin AUC7. One patient relapsed at 22 months and died of bleomycin pneumonitis 2 months after achieving a complete response with BEP chemotherapy. Neither RTI (present in 21.3%) nor tumor size >4 cm (in 43.3%) was predictive of relapse. Median follow-up was 106 months. At 15 years, outcomes were: relapse-free survival 99.4%, overall survival 91.4%, disease-specific survival 100%, subsequent malignant neoplasm rate 7.6%, and second testicular germ cell tumor rate 3.85%. One patient had persistent grade 1 thrombocytopenia at 46 months. CONCLUSIONS: These data add to the body of evidence that two cycles of carboplatin AUC7 is safe and effective adjuvant treatment for CS1 seminoma.
Carboplatin/administration & dosage , Neoplasm Recurrence, Local/epidemiology , Neoplasms, Germ Cell and Embryonal/therapy , Neoplasms, Second Primary/epidemiology , Seminoma/therapy , Testicular Neoplasms/therapy , Adult , Aged , Area Under Curve , Carboplatin/adverse effects , Carboplatin/pharmacokinetics , Chemotherapy, Adjuvant/adverse effects , Chemotherapy, Adjuvant/methods , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Administration Schedule , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Second Primary/prevention & control , New Zealand/epidemiology , Orchiectomy , Retrospective Studies , Seminoma/diagnosis , Seminoma/mortality , Testicular Neoplasms/diagnosis , Testicular Neoplasms/mortality , Young Adult
PIK3CA mutations resulting in disinhibition of the phosphoinositide 3-kinase (PI3K) pathway are present in approximately a third of estrogen receptor (ER)-positive breast cancer. Recent clinical trials of PI3K inhibition in PIK3CA-mutated metastatic breast cancer have shown improvement in progression-free survival of up to 11 months. We report a 68-year-old woman with metastatic ER-positive breast cancer with PIK3CA mutation who despite having disease progression after four lines of endocrine therapy (ET) attained a complete response (CR) after subsequent addition of a PI3K inhibitor. Remarkably, her CR is still maintained at 5 years. We believe this may be due to the co-occurrence of an NF1 mutation, which increases sensitivity to PI3K inhibition. Our case demonstrates restoration of sensitivity to ET by additional inhibition of PI3K, which resulted in exceptional disease response, far exceeding the expected duration. Hence, we believe that PI3K inhibition in addition to ET should be considered in patients with simultaneous PIK3CA and NF1 mutations.
