Genexol-PM is a biodegradable cremophor EL-free polymeric micelle formulation of paclitaxel. Here,we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment. In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² with 5 area under the curve carboplatin every 3weeks (6 cycles). The primary endpointwas the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR). Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00±0.00 mg/m² Genexol-PM or 174.24±3.81 mg/m² Genexol. Median followup was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (noninferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p= 0.148). Peripheral neuropathy of ≥ grade 3 occurred in one patient receiving Genexol. All toxicities were manageable. Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes.

Kim YM, et al. J Gynecol Oncol. 2018 Aug;30:e32. https://doi.org/10.3802/jgo.2019.30.e32

Background: Ten cancer patients (Six renal cell carcinoma and four breast cancer patients) were treated in a phase I/II study with a vaccine composed of autologous dendritic cells (DCs) and IL-2 to evaluate the DC vaccine-related toxicity and antigen-specific immune alteration. Methods: Cancer patients were treated twice with autologous CD34⁺ hematopoietic stem cell-derived, GM-CSF/IFN-γ-differentiated DCs pulsed with autologous tumor lysate and KLH, by 4-week interval. Following each subcutaneous injection of therapeutic DCs, low-dose (200 MIU) IL-2 was introduced for 14 consecutive days as an immune adjuvant. To determine the DC vaccine-induced immunological alterations, the KLH-specific lymphocyte proliferation, number of IFN-γ secreting T cells (ELISPOT assay), NK activity and the cytokine modulation were measured. Results: Cultured-DCs expressing HLA-DR, CD11c, CD83, and B7.1/B7.2 produced IL-12p70. After vaccination, the patients tolerated it. Clinical response was observed in one RCC patient as stable disease. However DC-vaccine related antigen-specific immune responses including peripheral blood lymphocyte proliferation and the number of IFN-r secreting cells were induced in six patients without clear correlation with clinical responses. Also NK activity was induced significantly in six patients after vaccination. DC vaccine-related decrease of TGF-β level or increase of IL-12p70 level and decline of CD4⁺CD25⁺ T cells were observed in three patients. However only in the RCC patient whose disease stabilized, combination of stimulatory as well as inhibitory immune alterations including induction of IFN-γ secreting T cell with reduction of CD4⁺ CD25⁺ T cell were correlated with clinical responses. Conclusion: Data indicated that DC vaccine combined with IL-2 is well tolerated without major side effects. DC vaccine induced the specific immunity against introduced antigen. Combinatorial alterations of immunological parameters indicating antigen-specific immune induction along with reduction of inhibitory immunity were correlated with clinical responses in DC vaccine treated patients.

Min KJ, et al. J Gynecol Oncol. 2015 Jul;26(3):232-239. https://doi.org/10.3802/jgo.2015.26.3.232

While ovarian cancer (OvCa) responds well to surgery and conventional chemotherapy, a high recurrence rate of advanced OvCa is observed. In this phase I/II study, 10 OvCa patients with minimal residual disease were treated with autologous dendritic cells (DCs) and IL-2 to evaluate the safety and feasibility of this therapeutic strategy and to characterize the antigen-specific immune alterations induced through this treatment. Approximately 4 months after initial debulking and chemotherapy, patients received two subcutaneous doses of autologous monocyte-derived DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH) at 4-week intervals. After each DC inoculation, low-dose (200 mIU) IL-2 was introduced for 14 consecutive days as an immune adjuvant. The vaccination was well tolerated. In three out of 10 patients, the inclusion status after the initial therapy showed the maintenance of complete remission (CR) after DC vaccination for 83, 80.9 and 38.2 months without disease relapse. One patient with stable disease (SD) experienced the complete disappearance of tumor after DC vaccination, and this status was maintained for 50.8 months until tumor recurrence. In two patients with partial response (PR) was not responding to DC vaccination and their disease recurred. In the three patients with disease free long-term survival, significant immune alterations were observed, including increased natural killer (NK) activity, IFN-γ-secreting T cells, immune-stimulatory cytokine secretion and reduced immune-suppressive factor secretion after DC vaccination. Thus, in patients with NED status and increased overall survival, DC vaccination induced tumor-related immunity, potentially associated with long-term clinical responses against OvCa.

Objective. To investigate the efficacy of conization followed by conservative management for treating stage IA1 microinvasive carcinoma of the uterine cervix. Design/Setting. Retrospective study. Population. Seventy‐five patients treated for stage IA1 microinvasive carcinoma of the cervix. Patients underwent conization followed by hysterectomy (Group 1, 53 patients), or were followed by conservative management (Group 2, 22 patients). Methods. Medical and histopathological record review. Results. For Group 1, pathology results showed that 30 had no residual tumor, one had cervical intraepithelial neoplasia (CIN) I, 11 had CIN III/cervical carcinoma in situ (CIS), nine had microinvasive carcinomas, and one had an invasive carcinoma (outcome for one patient not recorded). For Group 2, secondary procedures involved only cervical smears for 12 (48%) patients, of whom nine had normal cytology, one had low‐grade squamous intraepithelial lesion and two had high‐grade squamous intraepithelial lesions. For 13 (52%) patients in Group 2, secondary procedures involved repeat conization on whom six had no residual tumor, one had CIN II, four CIN III/CIS, and two microinvasive carcinoma and a negative resection margin. Therefore, conization followed by conservative management was an effective treatment for 90.9% (20/22) of Group 2. In neither group was recurrence recorded. There was no relation between lymphovascular invasion and follow‐up cytology or pathology results, or between resection margin status and follow‐up examination results. Conclusion. Conization alone with careful follow‐up appears to be an effective and safe treatment for patients with stage IA1 microinvasive carcinoma of the uterine cervix, regardless of resection margins status or lymphovascular invasion.