Jaime Espinós

Dendritic cell vaccination in glioblastoma after fluorescence-guided resection

AIM To assess whether the addition of a customized, active immunotherapy to standard of care including fluorescence-guided surgery, may provide hints of an improved survival for patients with poor-prognosis, incurable glioblastoma multiform. METHODS Preliminary to our ongoing, phase-II clinical trial, we conducted a small pilot study enrolling five consecutive patients with resectable glioblastoma. In terms of Recursive Partitioning Analysis, four patients were class V and one was class IV. In all five cases, fluorescence-guided surgery was employed, followed by rapid steroid discontinuation. Patients were then treated with a combination of standard radio-chemotherapy with temozolomide and tumor lysate-pulsed, mature dendritic cell-based vaccinations. RESULTS Though all five patients ultimately progressed, with any further treatment left to the sole decision of the treating oncologist, active immunotherapy was very well tolerated and induced specific immune responses in all three patients for whom enough material was available for such an assessment. Median progression-free survival was 16.1 mo. Even more important, median and mean overall survival were 27 mo and 26 mo, respectively. Three patients have died with an overall survival of 9 mo, 27 mo and 27.4 mo, while the other two are still alive at 32 mo and 36 mo, the former receiving treatment with bevacizumab, while the latter has now been off therapy for 12 mo. Four of five patients were alive at two years. CONCLUSION Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-II study is ongoing to possibly improve further on our very encouraging clinical results.

A phase II trial of less than 7 weeks of concomitant cisplatin-paclitaxel chemoradiation in locally advanced cervical cancer.

Objectives: This study was undertaken to determine the tolerability of a 7-week schedule of external beam radiation therapy, high-dose-rate brachytherapy, and weekly cisplatin and paclitaxel in patients with locally advanced carcinoma of the cervix. Methods: Twenty-nine patients with International Federation of Gynecology and Obstetrics stages IB2 to IVa cervical cancer were treated with 40 mg/m2 per week of intravenous (i.v.) cisplatin and 50 mg/m2 per week of i.v. paclitaxel combined with 45 Gy of pelvic external beam radiation therapy and 30 Gy of high-dose-rate brachytherapy. Results: Eleven patients (37.9%) were able to complete the 6 scheduled cycles of chemotherapy. The median number of weekly chemotherapy cycles administered was 5 (range, 2-7). Thirty-five (20.1%) of 174 cycles of chemotherapy were not given because of toxicity. The median dose intensity of cisplatin was 31 mg/m2 per week (95% confidence interval [CI], 25.2-36.8); that of paclitaxel was 44 mg/m2 per week (95% CI, 39.9-48.3). Twenty-two patients (78.6%) were able to complete the planned radiation course in less than 7 weeks. Median radiation treatment length was 45 days (95% CI, 43.4-46.6). After a median follow-up of 48 months, 7 patients (24.1%) experienced severe (Radiation Therapy Oncology Group grade 3 or higher) late toxicity. No fatal events were observed. Seven patients have failed, 1 locally and 6 at distant sites. The 8-year local/pelvic control rate was 95.7%, and the 8-year freedom from systemic failure rate was 76.1%. Eight-year actuarial disease-free survival and overall survival were 63.1% and 75.9%, respectively. Conclusions: This study demonstrated unacceptable toxicity of combining the stated doses of concurrent cisplatin and paclitaxel chemotherapy with definitive radiotherapy for patients with advanced cervical cancer. Additional phase I/II trials are recommended to clearly establish the recommended phase II dose for these drugs.

Hepatic breast cancer dissemination after an iatrogenic hepatic laceration during talc pleurodesis: a case report

Background Talc pleurodesis is an effective treatment for malignant pleural effusion. We present a case of an asymptomatic hepatic laceration that occurred during pleurodesis in a breast cancer patient and led to hepatic tumor dissemination. Discussion Pleurodesis is a relatively safe procedure, although previous studies have described malignant invasion of scar tissue. Conclusion To our knowledge, this is the first case report of tumor spread due to a liver puncture during talc pleurodesis in a breast cancer patient.

Combination of pegylated liposomal doxorubicin plus gemcitabine in heavily pretreated metastatic breast cancer patients: Long-term results from a single institution experience

The combination of Pegylated Liposomal Doxorubicin (PLD) plus Gemcitabine (GEM) has been previously investigated in the treatment of metastatic breast cancer (MBC). PLD is a doxorubicin formulation with prolonged circulation time and better tissue distribution. GEM is a nucleoside analog with nonoverlapping toxicity compared to PLD. The aim of our study was to assess efficacy, toxicity, and long‐term outcome of this combination. Patients with heavily treated MBC were retrospectively analyzed. Chemotherapy consisted of PLD 25 mg/m2 and GEM 800 mg/m2 day 1, on a three‐week schedule. Cardiac function was evaluated baseline and during treatment. Radiological response was graded according to RECIST criteria v1.1. Toxicity was scored according to CTCAE v4.0. Progression‐free survival (PFS) and overall survival (OS) were evaluated. From 2001 to 2014, 122 pts were included. Median age was 55 (range: 28‐84). Median previous treatment schedules in the metastatic scenario were 3 (range: 1‐15). Most patients received prior anthracyclines (85%). Median number of metastatic sites was 2 (range: 1‐7). Median number of cycles delivered was 5 (range: 1‐36). Overall response rate was 31% (5% complete responses; 26% partial responses). Stable and progressive diseases were observed in 32% and 26% of patients. Grade ≥3 neutropenia was observed in 29 patients (24%). Grade ≥3 hand‐foot syndrome was detected in 17 patients (14%), mostly since cycle 3 (88%). Median cumulative PLD dose was 125 mg/m2. At a median follow‐up of 101 months, median PFS and OS were 7 and 22 months, respectively. PLD‐GEM combination achieves remarkable long‐term outcomes with an acceptable toxicity profile in patients with MBC.

Abstract P4-13-04: Autologous dendritic cells vaccines combined with neoadjuvant chemotherapy increase total pCR in stages II-III non-overexpressing HER2 breast cancer patients and induce phenotypic changes in peripheral blood

Background Based on the synergistic effect between immuno- and chemotherapy (CT), we have elaborated an autologous vaccine with dendritic cells loaded with patients´ own tumor antigens (lysate), and we have already demonstrated that the addition of the vaccines to a standard neoadjuvant CT schedule has increased total pCR (breast+ axilla) in stages II-III non-overexpressing HER2 breast cancer patients (Santisteban M, SABCS 2012). Both cohorts, the control (C) and the vaccinated (V) were well balanced related to demographic characteristics. Toxicity has been similar in both the C and the V cohorts. Moreover, we have analyzed the phenotypic changes in peripheral blood induced by the vaccine and its correlation with pathologic responses. Indeed, we have studied if the amount of lysate used to load the dendritic cells or the total dendritic cell numbers received by the patients in the first five doses (before surgery) is correlated with pCR Methods Twenty-eight patients with stage II-III HER2 negative breast cancer have started on sequential neoadjuvant CT based on dose dense antracyclines (E 100mg/m2 and C 600 mgr/m2) x4 cycles plus GM-CSF followed by taxanes (DOC 75-100 mgr/m2) x4 cycles plus vaccination. The C historic cohort was composed of thirty patients who received the same treatment except for the absence of the vaccines. Vaccine calendar was started after the 4th EC and alternated with DOC and as maintenance up to a maximum of a 2 year-period. The first 5 vaccines were administered before breast surgery. Changes in different lymphocytes populations were measured in peripheral blood of patients at different points by flow cytometry (absolute cell counts). To date, twenty-one patients have both determinations of lymphocyte subpopulations before the 1st and the 6th vaccine. Paired samples t -tests and Fisher exact were used Results pCR was superior in the V cohort (24% versus 3.3%, p = 0.04). Lymphocyte subpopulations were measured in peripheral blood (cells/uL) and a stimulation of the immune system was found after the 5 vaccines schedule at the time of surgery as follows: NK (p<0.001), T cytotoxic CD8 (p = 0.018), T helper CD4 (p = 0.04), CD19 (p = 0.001), HLADRCD8 (p = 0.007), CD16CD8 (p = 0.003), HLADRCD4 (p<0.001), CD16CD4 (p = 0.008) and T regulators lymphocytes (p = 0.004). We did not find any differences among CD57CD8 (p = 0.17), CD56CD8 (p = 0.11), CD57CD4 (p = 0.45) and CD56CD4 (p = 0.65). We neither see correlation among the amount of lysate to load dendritic cells and the tpCR (p = 0.09) nor the amount of dendritic cells (summatory of 5 vaccines) administered intradermally and the pCR (p = 0.59) Conclusions Immunotherapy added to standard neoadjuvant CT could improve total pCR in stage II-III non-overexpressing HER2 breast cancer patients. After 5 doses of vaccination plus chemotherapy, we can observe phenotypic changes in peripheral blood: some immune system subpopulations increased statistically after the treatment in vaccinated patients. Neither the amount of lysate nor the number of dendritic cells used in the five first vaccines significantly correlated with the pRC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-13-04.

Pegylated liposomal doxorubicin (PLD) and gemcitabine in the treatment of metastatic breast cancer: A single-institution experience.

e11510 Background: We retrospectively analyzed the efficacy and safety of the combination of PLD and gemcitabine in patients (pt) with metastatic breast cancer (MBC) treated in our institution. Methods: We identified in our database 51 women diagnosed of MBC and treated with PLD on day 1 plus gemcitabine days 1 and 8 every 21 days between July 2000 and August 2009. Results: Median age was 59 years (range 32-83). Histologically 82.4% were ductal carcinomas, 68.6% expressed estrogen receptor and 29.4% overexpressed HER2. The median of previous chemotherapy regimens was 2 (range 0-8). 78.4% pt received previous anthracyclines, 82.4% taxanes, 54.9% capecitabine and 16.7% trastuzumab. 2 pt had previously received PLD and 3 gemcitabine. Median number of metastatic sites was 3 and the most frequent sites were: bone 70.6%, liver 56.9%, lung 37.3% and lymphatics 25.5%. Median PLD dose was 25mg/m2 (range 15-45 mg) and median gemcitabine dose was 800mg/m2 (range 650-1,000 mg). Median number of cycles was 8 (CI95%: 1...