Bioequivalence of a hybrid pegylated liposomal doxorubicin hydrochloride injection and Caelyx®: A single-dose, randomized, multicenter, open-label, two-period crossover study in patients with advanced ovarian cancer.

OBJECTIVE: To evaluate the bioequivalence of a hybrid pegylated liposomal doxorubicin (PLD) hydrochloride injection with reference product Caelyx®. METHODS: This multicenter, open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover, bioequivalence study was conducted in female patients aged ≥18 years and ≤75 years with ovarian cancer, whose disease progressed or recurred after platinum-based chemotherapy, and who were scheduled to start PLD therapy. Patients were intravenously infused drugs over 1 h at 50 mg/m2 dose two hours after breakfast on the first day of the chemotherapy cycle in period-I and crossed over to the other arm in period-II (day 29). Pharmacokinetic (PK) analyses were performed using two separate, validated liquid chromatography-mass spectrometry methods for encapsulated and unencapsulated doxorubicin. RESULTS: Both the test and reference formulations were well-tolerated and safe. The pharmacokinetic analysis for both encapsulated and unencapsulated doxorubicin was conducted in 50 patients and PK parameters were found to be comparable between test and reference products. The geometric mean ratios (90% confidence interval) of hybrid PLD/Caelyx® were; maximum measured plasma concentration (Cmax): 91.94-97.28%, area under the plasma concentration versus time from time 0 to t (AUC0-t): 95.19-103.67%, AUC from time 0 to ∞ (AUC0-∞): 95.13-103.66% for encapsulated doxorubicin and for unencapsulated doxorubicin Cmax: 92.08-116.46%, AUC0-t: 91.91-108.28%, AUC0-∞: 93.45-110.05%. CONCLUSION: The PLD formulation was found to be bioequivalent to Caelyx®.

Real-World Outcomes of Hodgkin Lymphoma: A Multi-Centric Registry From India.

BACKGROUND: Hodgkin's lymphoma (HL) is one of the most curable malignancies with a 5-year survival of over 80%. Most published literature from low-middle income countries comes from single institute experience. METHODOLOGY: The OncoCollect Lymphoma group registry was set up in 2017 and has 9 major participating sites across India. Data of newly diagnosed classical HL (CHL) patients, treated between 2011 and 2017, were collected using OncoCollect software. The clinical features, subtypes, prognostic stratification, treatment patterns, response to first-line treatment, and 5-year outcomes were analyzed. All statistical analysis was done using Microsoft R Open statistical software linked to OncoCollect software. RESULTS: There were 939 newly diagnosed CHL patients with a median age of 38 (range, 18-99) years at presentation. The male-to-female ratio was 2.07:1. Histological subtypes included mixed cellularity, CHL (MC, CHL), nodular sclerosis, CHL (NS, CHL), lymphocyte-rich, CHL (LR, CHL), and lymphocyte-depleted, CHL (LD, CHL), in 60.60%, 26.94%, 9.80%, and 2.66%, respectively. At presentation, 50.43% had B symptoms and 53.35% had advanced disease. 29.71% of advanced-stage patients had high Hodgkin IPI score. 79% and 21% of patients received 1st-line treatment with chemotherapy alone or combined modality treatment with chemotherapy and radiotherapy. The most common first-line chemotherapy was ABVD-based regimen (94.68%). The overall response rate was 93.48%. Complete response rates among early-stage favorable and unfavorable risk groups were 92.73% and 86.79%, and those among advanced-stage low- and high-risk groups were 76.64% and 69.78%, respectively. The median relapse-free follow-up duration was 51 months (IQR 22-69). A significant difference was found in 5-year EFS between the early- and advanced-stage disease 83.53% and 73.55% (p = 0.00087), respectively. Similarly, significant difference was found in EFS among early-stage patients treated with a combination of 4-cycle chemotherapy and radiotherapy vs. chemotherapy alone 88.57% and 66.33% (p = 0.0042), respectively. CONCLUSIONS: In this large cohort from India, survival of patients with HL was comparable to the developed world. With a median follow-up of 51 months, the 5-year EFS and OS of all patients were 78.24% and 83.63%, respectively.

Autologous stem cell transplantation for multiple myeloma: Long-term results.

BACKGROUND: Survival of myeloma patients has improved considerably in the past decade. However, limited data are available on their long-term outcome. We analysed the data of 225 consecutive patients who underwent autologous stem cell transplantation (ASCT) at our centre. METHODS: Between April 1990 and December 2013, a total of 225 patients with multiple myeloma (median age 53 years, range 27-67 years, 69.3% men) underwent ASCT. High-dose melphalan 200 mg/m2 was used for conditioning. Before transplant, the patients received induction therapy with novel agents (thalidomide and dexamethasone, or lenalidomide and dexamethasone, or bortezomib and dexamethasone); or vincristine, doxorubicin, dexamethasone; or alkylating agents (vincristine, melphalan, cyclophosphamide and prednisolone; or melphalan and prednisolone). The response to transplant was evaluated using the European Bone Marrow Transplant criteria, and an intention-to-treat analysis was done. RESULTS: Four-fifths (79.6%) of our patients had Durie Salmon Stage (DSS) IIIA and nearly a quarter (24%) of them had International Stage III disease. Before the transplant, 80.4% of patients had chemosensitive disease. The median interval from diagnosis to transplant was 10 months (range 2-128 months). Following ASCT, 197 (87.5%) patients responded. Complete response was obtained in 54.7%, very good partial response in 19% and partial response in 13.8%. At a median follow-up of 90 months (range 18-266 months), the median progression-free survival (PFS) and overall survival (OS) were 32 and 85.5 months, respectively. The estimated PFS and OS at 10 years were 29.7% and 43.6%, respectively. On multivariate analysis, the presence of extramedullary disease (HR 3.05, p < 0.001), and ISS III (HR 0.50, p < 0.02) predicted inferior OS. Extramedullary disease at diagnosis (HR 1.585, p < 0.03), and more than one regimen pre- transplant (HR 0.53, p < 0.02) predicted an inferior PFS. Complete response was a predictor of superior OS and PFS (p < 0.001). CONCLUSION: Complete response following ASCT is associated with good long-term outcome. Alternative treatment strategies are needed to improve results in patients who fail to achieve CR post-transplant and in those with high-risk disease.