Purpose Dose-dense chemotherapy improves survival but with increased toxicity and treatment-related cost. We report the prevalence of anemia and the possible risk factors associated with chemotherapy-related anemia and determine the cost and time-delay associated with transfusion requirement in Indian patients with non-metastatic breast cancer on dose-dense preoperative chemotherapy. Methods In this study, triple-negative breast cancer (TNBC) patients were treated preoperatively with docetaxel and cyclophosphamide alternating with epirubicin and cisplatin every 2 weeks. Patients were evaluated for anemia pre- and post-chemotherapy. We examined trends in the red cell indices, transfusion requirement, time to transfusion, as well as risk factors associated with transfusion during treatment, along with delay in treatment due to anemia and the additional cost incurred. Results A total of 116 consecutive women with nonmetastatic TNBC were treated with preoperative chemotherapy. The median age was 44.5 years. 56.1% of patients had stage III disease. Anemia was detected at baseline in 54 (46.5%) patients with mild anemia (10–12 g/dl) in 42 (36.2%) patients and moderate anemia (8–10 g/dl) in 12 (10.3%) patients. During the course of treatment, all patients developed anemia. A total of 44 patients (37.9%) required transfusion during chemotherapy, with 55(47.4%) patients developing grade 1–2 anemia and 40 (34.5%) patients developing grade 3 anemia. The factors associated with anemia requiring transfusion were a steeper decline in hemoglobin after two cycles (OR 1.65, p = 0.02), low-grade tumor (OR 2.48, p = 0.03), and thrombocytopenia grade 3 or 4 (OR 4.35, p = 0.034), of which tumor grade and thrombocytopenia remained significant in multivariate analysis. Nearly one-fourth of the study population had a delay between two cycles of chemotherapy due to anemia. A median additional cost of INR 7000 was incurred among those requiring blood transfusion. Conclusion Anemia is a common toxicity associated with dose-dense chemotherapy during curative breast cancer treatment leading to delay in treatment and increased cost. Low-grade tumor, grade 3 or 4 thrombocytopenia, and grade 2 or higher anemia after two cycles of chemotherapy are risk factors for blood transfusions during treatment.
Palbociclib is a cyclin dependent kinase (CDK) 4/6 inhibitor that is indicated in combination with an aromatase inhibitor for first-line treatment of hormone receptor-positive, human epidermal growth factor receptor 2 -negative advanced or metastatic breast cancer. The commonly described side effects of palbociclib are neutropenia, anaemia, thrombocytopenia, fatigue, nausea, stomatitis, alopecia, diarrhoea, decreased appetite, vomiting, asthenia, peripheral neuropathy and epistaxis. However, post approval, increasing use of this drug has revealed another potentially fatal complication, in the form of pneumonitis, especially in the Asian population. The PALOMA 3 trial showed that rates of grade 3 and grade 4 adverse events were modestly higher in Asians than non-Asians, though palbociclib exposure was similar in both races. From this, we could infer that adverse effects of this drug must be monitored more specifically in individual racial populations. We report a patient who developed pneumonitis while on palbociclib and discuss the possible mechanisms and management of CDK 4/6 inhibitor-related lung injury.
Purpose: Dose dense chemotherapy improves survival but also increases toxicity and treatment related cost. Here we report the prevalence of anemia, understand the risk factors of chemotherapy related anemia and determine the cost and time-delay associated with transfusion requirement in Indian non-metastatic breast cancer patients on dose dense preoperative chemotherapy.Methods: In this study, 116 triple negative breast cancer (TNBC) patients were treated preoperatively with Docetaxel and Cyclophosphamide alternating with Epirubicin and Cisplatin every 2-weekly. Patients were evaluated for anemia pre- and post-chemotherapy. We examined trends in the cell counts, transfusion requirement, time to transfusion as well as risk factors associated with transfusion during treatment, along with delay in treatment due to anemia and the additional cost incurred.Results: One hundred and sixteen women with high-risk non-metastatic TNBC were treated. Median age was 44.5 years. 56.1% had stage III disease. Delivery of 6/8 planned doses was achieved in 98.3% of patients, and all 8 doses in 86% patients. Anemia was detected at baseline in 54(46.5%) patients with mild(10-12g/dl) anemia in 42(36.2%) patients and moderate(8-10g/dl) in 12(10.3%) patients. Forty-four patients (37.9%) required transfusion during chemotherapy with 55(47.4%) patients having grade 1-2 anemia and 40(34.5%) patients having grade 3 anemia. The factors associated with transfusion were low grade of tumor (OR 2.48 (95% CI 1.08 - 5.68), p = 0.025), hemoglobin post 2 cycles of chemotherapy (OR 1.74 (95% CI 1.21- 2.51), p = 0.003), thrombocytopenia grade 3 or 4 (OR 4.35 (95% CI 1.062-17.827), p = 0.034) and drop in hemoglobin after 2 cycles (OR 1.65 (95% CI 1.09-2.48), p = 0.017). Nearly one fourth of the study population had a delay between two cycles of chemotherapy due to anemia. A median additional cost of Rs 7000 (IQR-Rs 7000 – Rs 14000) was incurred on transfusion.Conclusion: Anemia is a common toxicity associated with dose dense chemotherapy during curative breast cancer treatment leading to delay in treatment and increased cost. Low grade tumor, grade 3 or 4 thrombocytopenia and Grade 2 or higher anemia after 2 cycles of chemotherapy are risk factors for blood transfusions during treatment.
Purpose Carboplatin-containing treatment regimens in early TNBC have shown improved pCR(pathological complete response) and better EFS(event-free survival) but at the expense of increased toxicity, often leading to compromised delivery of planned treatment. We aimed to evaluate a novel alternating regimen to incorporate platinum in early TNBC. Methods We analyzed the data of women with early TNBC who were treated with four cycles each of docetaxel(D;75 mg/m2) and cyclophosphamide(C;600 mg/m2) alternating with cisplatin(P;60 mg/m2) and epirubicin(E;90 mg/m2) (ddDCEP) given every two weeks over a duration of 16 weeks. Pathological complete response was the primary endpoint assessed, along with treatment delivery, adverse events, and survival. Results A total of 116 women with stage I-III TNBC received neoadjuvant ddDCEP. Pathological complete response(pCR) defined as no residual invasive cancer in both breast(T0/Tis) and axilla(N0), was observed in 55.2% of all evaluable patients. The proportion of pCR in stage I/II disease was 62.2%, and stage III was 49.5%. 37.9% of patients developed grade 3 anaemia. Grade 3/4 neutropenia occurred in 16.3%, and febrile neutropenia in 4.3% of patients. 86% of patients completed all 8 cycles of chemotherapy, and 98% at least 6 out of 8 cycles. 12% of patients required a dose reduction of taxane, 13% for epirubicin, and 19% for platinum. The proportion of patients requiring dose reduction and the average total dose reduction was significantly higher in the pCR compared to the no pCR group for cisplatin and epirubicin. At 2 years of median follow-up, the recurrence-free survival was 91.2%, and overall survival was 97%. Conclusion In non-metastatic TNBC, treatment with ddDCEP as neoadjuvant therapy resulted in a high pCR(55.2%) proportion allowing good delivery of all planned therapy with manageable toxicity.
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