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Autologous dendritic cell (DC)-based immunotherapy is a cell-based advanced therapy medicinal product (ATMP) that was first introduced more than three decades ago. In the current study, our objective was to establish a harmonized protocol using two varied antigenic sources and a good manufacturing practice (GMP)-compliant, manual method for generating clinical-grade DCs at a limited-resource academic setting. After obtaining ethical committee-approved informed consent, the recruited patients underwent leukapheresis, and single-batch DC production was carried out. Using responder-independent flow cytometric assays as quality control (QC) criteria, we propose a differentiation and maturation index (DI and MI, respectively), calculated with the QC cut-off and actual scores of each batch for comparison. Changes during cryopreservation and personnel variation were assessed periodically for up to two to three years. Using our harmonized batch production protocol, the average DI was 1.39 and MI was 1.25. Allogenic responder proliferation was observed in all patients, while IFN-gamma secretion, evaluated using flow cytometry, was detected in 10/36 patients and significantly correlated with CD8+ T cell proliferation (p value-0.0002). Tracking the viability and phenotype of cryopreserved MDCs showed a >90% viability for up to three years, while a mature DC phenotype was retained for up to one year. Our results confirm that the manual/semi-automated protocol was simple, consistent, and cost-effective, without the requirement for expensive equipment and without compromising on the quality of the final product.
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INTRODUCTION: Cervical cancer is the third most common cancer in India. There is limited data on the treatment of relapsed cervical cancer from India; therefore, we report the outcomes of patients with recurrent cervical cancer who were treated with palliative chemotherapy (CT). MATERIALS AND METHODS: This was a retrospective study of patients with recurrent cervical cancer who received palliative CT from January 2012 to December 2016. The demographic details, clinical profile and survival outcomes were collected. Patients were treated with carboplatin or paclitaxel and carboplatin. Local radiation was given for symptomatic patients. Patients were assessed for responses clinically and/or radiologically after three and six cycles of CT. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Forty-six patients with recurrent cervical cancer were included in this analysis, with a median follow-up of 9.4 months. The median age was 49.5 (25-65) years and the median disease-free interval was 31.3 (2-196) months. Biopsy confirmation of relapse was established in 63%. The median number of CT cycles was six. Twenty-four (52.2%) patients completed six cycles of CT. The overall response rate was 56.5%. Patients with a complete or a partial response were more likely to have PFS > 6 months (p < 0.0001). Median PFS and OS were, respectively, 8.4 (95% CI 6.1-10.7) months and 10.3 (95% CI 6.8-13.8) months. The completion of all cycles of CT and the site of metastasis (nodal vs. visceral or combined) were found to be associated with OS. CONCLUSION: Palliative CT with paclitaxel carboplatin is a safe and effective option in Indian patients with recurrent cervical cancer, with more than half of the patients completing the prescribed CT. Further prospective trials may be required to place this treatment in the right context, in this era of immunotherapy and targeted therapy. However, knowing the outcomes in our population and prognostic factors will help in better prognostication of patients, thereby channelling our limited resources where necessary.
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Background There is limited data on specific antiemetic protocols for control of chemotherapy-induced nausea/vomiting (CINV) caused by weekly cisplatin regimens. Olanzapine is an active agent against CINV and may offer better control of nausea compared to aprepitant/fosaprepitant-based regimens. The usual antiemetic dose of olanzapine (10 mg for four days) causes problems with drowsiness. A lower dose may be as effective with lesser side effects in patients receiving weekly cisplatin. Objective To assess the control of nausea, vomiting, and occurrence of side effects with a modified olanzapine-based antiemetic regimen among patients with carcinoma of the cervix receiving concurrent cisplatin with pelvic radiotherapy. Setting Tertiary cancer hospital in Southern India. Methods We used a modified regimen "mini-OPD", oral olanzapine (5 mg) days 1 and 2, intravenous palonosetron (0.25 mg) and dexamethasone (12 mg) on day 1 of cisplatin administration in patients with carcinoma of the cervix receiving concurrent chemoradiotherapy with weekly cisplatin (40 mg/m2/week). At our centre, these patients remained inpatients throughout chemoradiotherapy. CINV-related outcomes were captured in the patients' records by the treating physician in the subsequent week (up to 6 times per patient depending on the number of cycles). We audited these records to calculate the complete response (CR defined as no emetic episodes and no use of rescue medication) rate. Main outcome measure Grades of nausea, vomiting, and drowsiness as per CTCAE v4.0. Results Data of 65 patients (median age: 48 years) who received mini-OPD regimen (median doses of cisplatin/patient: 4) was available. The CR rate was 55%. Considering all cycles together (217 weekly assessment points), "no nausea" target was attained in 125 (58%) assessments and "no vomiting" in 168 (77%). There were no significant side effects. Conclusions The mini-OPD regimen is an inexpensive, non-toxic and effective regimen for the prevention of CINV in patients receiving weekly cisplatin concurrent with pelvic radiotherapy.
