Docetaxel Regimen Research Articles

Docétaxel dans le cancer de prostate métastatique résistant à la castration chez l’octogénaire : analyse multicentrique de dix ans de pratique

There is very few data about the management of elderly patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to analyze the management of patients aged 80 and over treated with docetaxel for a mCRPC. Clinical and pathological characteristics of octogerians treated with docetaxel were collected retrospectively from 3 French centers from 2009 to 2019. Patient's outcome, treatments administered before and/or after docetaxel were also analyzed. Data of 89 patients could be analyzed. A total of 20.2% of patients received the standard regimen and 79.8% received an adapted one. Patients in the adapted group were significantly older than in standard one. Other patient's characteristics-including the geriatric scales-were similar. Dose reductions for toxicity were more frequent in the standard group (P=0.04). The median overall survival of the total population was 13.3 months. It was longer in the standard group than in the adapted group (26.1 months vs 12.4 months=0.01). In multivariate analysis, the type of docetaxel regimen (standard versus adapted) was an independent predictor of survival. This study suggests the benefit of the standard management even in oldest patients. A geriatric evaluation should certainly be processed in patients with poor oncogeriatric scale in order to select the sub-population able to receive the full dose standard docetaxel regimen.

Inhibiting PAD2 enhances the anti-tumor effect of docetaxel in tamoxifen-resistant breast cancer cells

BackgroundTamoxifen resistance presents a huge clinical challenge for breast cancer patients. An understanding of the mechanisms of tamoxifen resistance can guide development of efficient therapies to prevent drug resistance.MethodsWe first tested whether peptidylarginine deiminase 2 (PAD2) may be involved in tamoxifen-resistance in breast cancer cells. The effect of depleting or inhibiting PAD2 in tamoxifen-resistant MCF-7 (MCF7/TamR) cells was evaluated both in vitro and in vivo. We then investigated the potential of Cl-amidine, a PAD inhibitor, to be used in combination with tamoxifen or docetaxel, and further explored the mechanism of the synergistic and effective drug regimen of PADs inhibitor and docetaxel on tamoxifen-resistant breast cancer cells.ResultsWe report that PAD2 is dramatically upregulated in tamoxifen-resistant breast cancer. Depletion of PAD2 in MCF7/TamR cells facilitated the sensitivity of MCF7/TamR cells to tamoxifen. Moreover, miRNA-125b-5p negatively regulated PAD2 expression in MCF7/TamR cells, therefore overexpression of miR-125b-5p also increased the cell sensitivity to tamoxifen. Furthermore, inhibiting PAD2 with Cl-amidine not only partially restored the sensitivity of MCF7/TamR cells to tamoxifen, but also more efficiently enhanced the efficacy of docetaxel on MCF7/TamR cells with lower doses of Cl-amidine and docetaxel both in vivo and in vivo. We then showed that combination treatment with Cl-amidine and docetaxel enhanced p53 nuclear accumulation, which synergistically induced cell cycle arrest and apoptosis. Meanwhile, p53 activation in the combination treatment also accelerated autophagy processes by synergistically decreasing the activation of Akt/mTOR signaling, thus enhancing the inhibition of proliferation.ConclusionOur results suggest that PAD2 functions as an important new biomarker for tamoxifen-resistant breast cancers and that inhibiting PAD2 combined with docetaxel may offer a new approach to treatment of tamoxifen-resistant breast cancers.

815P - A new docetaxel (DOC)-based triplet regimen does not improve the outcome of metastatic (M) or locally advanced (LA) gastric cancer (GC) as compared with an epirubicin (EPI) standard triplet regimen: A GISCAD trial

BackgroundEOX (EPI + oxaliplatin-OHP + capecitabine-CAPE) is still one of the standard regimens for M or LA GC, but the role of EPI is today widely questioned and DOC replaced it in many institutions. A new DOC-based combination was developed with attempt at increasing efficacy/activity vs EOX without the heavy toxicity of the “classic” DOC regimen. MethodsFrom 1/2013 to 11/2018, 169 previously untreated patients (pts) with M (87,6%) or LA GC were randomized by 23 centers between low-TOX (arm A) and EOX (arm B): Arm A: DOC: 35mg/m2 iv, d 1 and 8 + OHP: 80mg/m2 iv, d 1 + CAPE: 750mg/ m2 x2 daily p.o. for 2 weeks Arm B: EPI: 50mg/m2 iv, d 1 +OHP: 130mg/m2 iv, d 1 +CAPE: 625mg/m2 x2 daily p.o. for 3 weeks Both regimens recycled q 3 weeks If no PD or heavy toxicity, pts were programmed on therapy for a maximum of 5 (if CR) or 6 courses (if PR or SD). The primary endpoint was PFS, the secondary OS, ORR, DCR and tolerability. The study was designed to detect a 35% (80% power at a two side 5% significance level) PFS increase with low-TOX and an interim analysis for futility was planned after the first 127 events (75% of expected). ResultsAt the cut-off date of interim analysis, 164 pts (median age 62 y; 63,9% male; ECOG PS: 0 in 75,7%) have available data for evaluation of primary efficacy analysis. The median PFS (KM) was 5.8 months (95% CI: 5.0 – 7.8) in arm A vs 6.5 months (95% CI: 5.0 – 8.9) in arm B, without statistical difference (NS). Also OS was comparable in the two arms: 12.2 (95% CI: 8.6 -16.0) vs 12.8 months (95% CI: 9.1-21.0). ORR were 22% and 35.4% and DCR 59.8% and 65.9%, respectively, again NS. The median number of courses per patient was 6 and treatment modification was higher in arm A (90,2% vs 78%) with a weakly higher number of AE with CTC ≥ 3 in arm A (54 vs 41). ConclusionsThese results indicate that, on the basis of the planned futility analysis, it is unlikely that low-TOX regimen is able to reach the target of improvement against EOX, both in efficacy/activity and in tolerability. Therefore, if the clinician’s choice is in favour of a triplet (i.e. in aggressive or very symptomatic disease), EOX could remain a standard option. Clinical trial identificationNCT02076594. Legal entity responsible for the studyGISCAD. FundingStudy carried out within the Rete Oncologica Lombarda-ROL project and founded as per the Deliberazioni di Giunta Regionale (DGR) di Regione Lombardia n° VIII/010761 dell’11-12-2009 e DGR IX/1485 del 30-03-2011”. DisclosureAll authors have declared no conflicts of interest.

796P - Randomised phase II trial of first-line docetaxel, carboplatin, capecitabine (CTX) and epirubicin, oxaliplatin, capecitabine (EOX) in advanced esophagogastric adenocarcinoma (SEED)

BackgroundChemotherapy is associated with a survival benefit in advanced gastric cancer. Several options exist, including EOX. The regimen docetaxel, cisplatin and 5-fluorouracil (DCF) is toxic and modifications have been developed. In our institution CTX was a standard treatment from 2004 to 2012 when it was replaced by EOX. Afterwards, a randomised trial with CTX was conducted. MethodsSEED was a prospective, single-center, phase 2 trial in unresectable HER2-negative esophagogastric adenocarcinoma. Patients were randomised to either docetaxel 60mg/m2, carboplatin AUC5 and capecitabine 1000mg/m2 bd for 14 days q4w (CTX) or epirubicin 50mg/m2, oxaliplatin 130mg/m2 and capecitabine 625mg/m2 bd for 21 days q3w (EOX). Treatment continued until progression, intolerance or a maximum of 9 cycles. The primary endpoint was 1-year-survival for patients treated with CTX. The trial sought to accept (lower boundary 55%) or reject (higher boundary 40%) CTX for further study without making direct comparisons to EOX. Secondary endpoints included OS, PFS and grade 3/4 toxicities. ResultsFrom 2014 to 2019 a total of 98 patients were randomised (49 in each arm). The median age was 63 (36 - 79). Male/female: 79/19; ECOG PS (0/1): 46/52; oesophageal/GEJ/gastric: 29/44/25; metastatic/non-metastatic: 96/2. As of 26 April 2019, 85 patients had died. The estimated 1-year survival was 32% (95% CI 19 - 46) for CTX and 39% (95% CI 25 - 52) for EOX. The median PFS and OS was 6.2 months (95% CI 5.2 - 7.2) and 9.2 months (95% CI 7.2 - 11.2), respectively, for CTX, and 5.2 months (95% CI 3.5 - 7.0) and 10.2 months (95% CI 7.9 - 12.4), respectively, for EOX. Grade 3/4 related toxicities in>5% were neutropenia (78%), febrile neutropenia (25%), diarrhoea (8%) and fatigue (6%) for CTX, and neutropenia (49%), febrile neutropenia (10%), peripheral neuropathy (8%) and nausea (8%) for EOX. There were no treatment-related deaths. ConclusionsCTX resulted in a 1-year-survival rate of 32% and so is rejected for further study. Also, CTX had a high rate of febrile neutropenia. CTX is not recommended for patients with esophagogastric cancer, except selected patients intolerant of other standard therapies, and then only with G-CSF support. Clinical trial identificationNCT02177552. Legal entity responsible for the studyLene Baeksgaard. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Immune-triggered cancer treatment by intestinal lymphatic delivery of docetaxel-loaded nanoparticle

The maximally tolerated dose (MTD) approach in conventional chemotherapy accompanies adverse effects, primarily due to high drug concentrations in the blood after intravenous administration and non-specific damages to highly proliferating cells, including immune cells. This causes the immune system to dysfunction. To rather boost intrinsic tumor-fighting immune capacity, we demonstrate a new oral route treatment regimen of docetaxel (DTX) without apparent toxicity. The DTX-loaded cationic solid lipid nanoparticles (DSLN-CSG) were coated with an anionic polymer conjugated with glycocholic acid. The resulting nanoparticles (DSLN-CSG, ~120 nm in diameter) were actively absorbed in the distal ileum mediated by interactions with the apical sodium bile acid transporter. The plasma DTX profile was sustained up to 24 h after a single oral dose and did not impair the functions of the immune system. In mouse models, daily oral DSLN-CSG administration inhibited the growth of existing tumors and tumor formation by medication prior to cancer cell inoculation. The extent of effects depended on the cancer cell lines of melanoma, colorectal adenocarcinoma, and breast carcinoma. It was most effective for melanoma in growth inhibition and in preventing tumor formation in mice. During the medication, the cytotoxic T cell population increased while the populations of tumor-associated macrophage and regulatory T cell declined. The low dose daily oral treatment may help patients with intermittent maintenance therapy between MTD cycles and prevent tumor recurrence after completing remission for certain tumors.

Risk factors for febrile neutropenia and effectiveness of primary prophylaxis with pegfilgrastim in patients with esophageal cancer treated with docetaxel, cisplatin, and 5-fluorouracil

BackgroundThe docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen is an effective form of chemotherapy for advanced esophageal cancer. However, the incidence of adverse events such as febrile neutropenia and hematological toxicity is high.MethodsAmong 937 patients with esophageal cancer at Toranomon Hospital between January 2011 and December 2018, 92 who underwent the DCF regimen as initial treatment were selected. We investigated the risk factors for febrile neutropenia in patients with esophageal cancer treated with DCF regimen and the effectiveness of pegfilgrastim as primary prophylaxis.ResultsAdverse events (CTCAE grade ≥ 3) were observed in 45 of the 92(48.9%) patients with esophageal cancer treated with an initial DCF regimen. Febrile neutropenia was observed in 20 (21.7%) patients. Non-use of pegfilgrastim (odds ratio = 16.393; 95% confidence interval 2.049–125.0) as primary prophylaxis was identified as an independent factor predictive of febrile neutropenia. The pegfilgrastim group had a significantly lower incidence of neutropenia than the control group (9.1% vs 61.0%; p < 0.001). The incidence of febrile neutropenia was 3.0% in the pegfilgrastim group and 32.2% in the control group (p = 0.001). In addition, the incidence of any adverse effect ≥ CTCAE grade3 was also significantly lower in the pegfilgrastim group (12.1% vs 69.5%; p < 0.001). The reduced/interruption rate of next DCF therapy was 6.1% in the pegfilgrastim group and 30.5% in the control group (p = 0.006).ConclusionThis study revealed that the non-use of pegfilgrastim was an independent factor predictive of febrile neutropenia in multivariate analysis. Pegfilgrastim as primary prophylaxis prevents severe neutropenia and febrile neutropenia in patients with esophageal cancer treated with the DCF regimen.

Results of randomized phase II trial of neoadjuvant carboplatin plus docetaxel or carboplatin plus paclitaxel followed by AC in stage I-III triple-negative breast cancer (NCT02413320).

516 Background: Addition of neoadjuvant carboplatin (Cb) to paclitaxel (T) followed by doxorubicin + cyclophosphamide (AC) improves pathologic complete response (pCR) rate compared to T/AC in TNBC. An anthracycline-free regimen of Cb plus docetaxel (D) also yields high pCR rates in TNBC, and patients achieving pCR with this regimen demonstrate excellent 3-year outcomes without adjuvant anthracycline. This study was designed to compare the efficacy of neoadjuvant regimens CbT→AC and CbD in TNBC. Methods: In this multicenter study, eligible patients with stage I–III TNBC were randomized (1:1) to either paclitaxel 80 mg/m2 every week X 12 + carboplatin (AUC 6) every 3 weeks X 4, followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 every 2 weeks X 4 (CbT→AC, Arm A), or to carboplatin (AUC 6) + docetaxel (75 mg/m2) every 21 days X 6 cycles (CbD, Arm B). The primary endpoint was pCR (no evidence of invasive tumor in the breast and axilla). The two regimens were compared for differences in pCR, residual cancer burden (RCB), treatment delivery, and toxicity. Results: Between 2015 and 2018, 100 patients were randomized; 48 to Arm A and 52 to Arm B. Median age was 52 years, median tumor size was 2.7 cm, 30% were lymph node-positive and 17% carried a BRCA1/2 mutation. Baseline demographic and tumor characteristics were balanced between two arms. pCR was 55% (95%CI: 41%-59%) in Arm A and 52% (95%CI: 39%-65%) in Arm B, p =0.84. RCB 0+1 rate was 67% in both arms. Grade 3/4 adverse events were more common in Arm A compared to Arm B (73% vs 21%, p &lt; 0.0001), with most notable differences in rates of G3/4 neutropenia (Arm A = 60%, Arm B = 8%, p = 0.0001), febrile neutropenia (Arm A = 18%, Arm B = 0%, p = 0.0001), and G3/4 anemia (Arm A = 46%, Arm B = 4%, p = 0.0001). 81% of Arm A patients completed all 4 doses of AC and 4 doses of Cb, and 71% completed &gt; 9 doses of T. 90% of Arm B patients completed all 6 doses of CbD (p = 0.034). Conclusions: The non-anthracycline platinum regimen of CbD yields pCR and RCB 0+1 rates similar to 4-drug regimen of CbTàAC, but with a more favorable toxicity profile and higher treatment completion rate. The CbD regimen should be further explored as a way to de-escalate therapy in TNBC. Clinical trial information: NCT02413320.

Cost-Effectiveness of Docetaxel and Paclitaxel for Adjuvant Treatment of Early Breast Cancer: Adaptation of a Model-Based Economic Evaluation From the United Kingdom to South Africa

ObjectivesTransferability of economic evaluations to low- and middle-income countries through adaptation of models is important; however, several methodological and practical challenges remain. Given its significant costs and the quality-of-life burden to patients, adjuvant treatment of early breast cancer was identified as a priority intervention by the South African National Department of Health. This study assessed the cost-effectiveness of docetaxel and paclitaxel-containing chemotherapy regimens (taxanes) compared with standard (non-taxane) treatments. MethodsA cost-utility analysis was undertaken based on a UK 6-health-state Markov model adapted for South Africa using the Mullins checklist. The analysis assumed a 35-year time horizon. The model was populated with clinical effectiveness data (hazard ratios, recurrence rates, and adverse events) using direct comparisons from clinical trials. Resource use patterns and unit costs for estimating cost parameters (drugs, diagnostics, consumables, personnel) were obtained from South Africa. Uncertainty was assessed using probabilistic and deterministic sensitivity analyses. ResultsThe incremental cost per patient for the docetaxel regimen compared with standard treatment was R6774. The incremental quality-adjusted life years (QALYs) were 0.24, generating an incremental cost-effectiveness ratio of R28430 per QALY. The cost of the paclitaxel regimen compared with standard treatment was estimated as −R578 and −R1512, producing an additional 0.03 and 0.025 QALYs, based on 2 trials. Paclitaxel, therefore, appears to be a dominant intervention. The base case results were robust to all sensitivity analyses. ConclusionsBased on the adapted model, docetaxel and paclitaxel are predicted to be cost-effective as adjuvant treatment for early breast cancer in South Africa.

Chemotherapy Regimen and Incidence of Malnutrition after Chemotherapy in Non-small Cell Lung Cancer

Lung cancer is the leading cause of death worldwide and in Thailand. The treatment of non-small cell lung (NSCLC) with chemotherapy might affected on nutritional status which could correlate with the treatment response and quality of life. Thus, the objectives of this research were to study the nutritional status of patients after chemotherapy and the incidence of malnutrition. This retrospective longitudinal descriptive study was gathering the information from medical records January, 2013 to December, 2014. A 114 patients were met the inclusion criteria which were completed 4 or 6 cycles of treatment. Body mass index (BMI) and percentage of weight loss were used to assess the nutritional status. Malnutrition was classified when BMI under 18.5 kg/m2 and weight change more than 5%. The average age, baseline weight and BMI were 60.4±10.1 year, 55.0±9.0 kg and 22.0±2.5 kg/m2, respectively. The incidence of malnutrition was 6.1%. Mean BMI decreased from 22.0 kg/m2 to 21.5 kg/m2 after chemotherapy. Patients treated with carboplatin plus paclitaxel showed the highest change of BMI (-0.6 kg/m2) and docetaxel regimen showed the highest incidence of malnutrition (18.8%). According to the base agents; taxane-based regimen showed the most effect on nutritional status and 85% of those patients were malnutrition. In conclusion, docetaxel and carboplatin plus paclitaxel highly affected on nutritional status. In patients treated with those regimens, they should be closely monitored and gave an adequate nutritional advice for the better treatment response, decrease the side effect from chemotherapy and improve patients’ quality of life.

A Dose-Escalating Pilot Study (NCT03017404) of Pegylated Liposomal Doxorubicin and Cyclophosphamide, Followed by Docetaxel Administration as a Neoadjuvant Chemotherapy Regimen in Patients with Locally Advanced Breast Cancer

Background: Pegylated liposomal doxorubicin (PEG-LD) has a comparable efficacy but a distinct toxicological profile compared with free doxorubicin. The use of PEG-LD and cyclophosphamide followed by docetaxel regimen as neoadjuvant chemotherapy has not been well established. Objectives: We aimed to assess the maximum tolerated dose (MTD) and toxicity of this regimen in patients with locally advanced breast cancer. Methods: A total of 19 patients were enrolled in this trial. In the initial treatment plan, patients were given PEG-LD at 35, 40, 45, or 50 mg/m² on day 1 during the first four cycles, and cyclophosphamide was administered at a dose of 600 mg/m². During the last four cycles, docetaxel was administered at 75 mg/m² on day 1 of a 21-day scheme. Results: The MTD was 40 mg/m² PEG-LD and 600 mg/m² cyclophosphamide administered on day 1 of a 21-day cycle. Dose-limiting toxicity, grade 3 hand-foot syndrome, was observed in one patient during level 2 and three patients during level 3. Other side effects included neutropenia, anemia, stomatitis, rash, nausea/vomiting, alopecia, transaminase elevation, and cardiotoxicity. The pathological complete response rate was 21.1%. Conclusions: Our study demonstrated that combination of 40 mg/m² PEG-LD and 600 mg/m² cyclophosphamide, followed by 75 mg/m² docetaxel on day 1 of a 21-day scheme, was an efficacious and well-tolerated neoadjuvant regimen for patients with locally advanced breast cancer.

Triplet chemotherapy with docetaxel, cisplatin and S-1 for unresectable advanced squamous cell carcinoma of the esophagus: phase I/II trial results

BackgroundAlthough triplet regimen of docetaxel, cisplatin, and 5-FU (DCF) reportedly yields high response rates for metastatic squamous cell carcinoma of the esophagus (SCCE), it has severe toxicity. In our previous phase II trial, grade 3/4 toxicities of neutropenia occurred in 68.8% of the patients. Development of chemotherapeutic regimen that does not impair quality of life of the patients with metastatic SCCE is therefore needed. A novel chemotherapeutic regimen combining docetaxel, cisplatin, and alternate-day administration of S-1 (modified DCS) may be associated with reduction of severe adverse effects.MethodsThis study is a single center phase I/II trial of chemotherapy using modified DCS regimen for patients with recurrent/unresectable SCCE. The phase I trial adopts a ‘3 + 3 patient cohort’, dose-escalating study design. In the phase II trial, the primary endpoint is evaluation of the overall response rate (ORR). Secondary endpoints are evaluation of drug-related toxicity, overall survival (OS), and progression-free survival (PFS).ResultsIn the phase I trial, the recommended dose for docetaxel, cisplatin, and S-1 were 40 mg/m2 (day 1), 50 mg/m2 (day 1), and 80 mg/m2/day, respectively. In the phase II trial (n = 50), the ORR was 54 %. The median OS and PFS were 10 and 4 months, respectively. Grade 3/4 adverse events included neutropenia (26%), leukopenia (14%), anorexia (10%) and febrile neutropenia (6%).ConclusionThe modified DCS therapy for patients with advanced SCCE is feasible and safe in both chemotherapeutic and perioperative periods.Registration number: UMIN000016364.

The Clinical Efficacy and Safety of Four-Weekly Docetaxel as First-Line Therapy in Elderly Lung Cancer Patients with Squamous Cell Carcinoma.

BackgroundDocetaxel is one of the standard treatments for advanced non-small cell lung cancer. Docetaxel is usually administered in a 3-week schedule, but there is significant toxicity. In this phase II clinical study, we investigated the efficacy and safety of a 4-weekly schedule of docetaxel monotherapy, as first-line chemotherapy for advanced squamous cell carcinoma in elderly lung cancer patients.MethodsPatients with stage IIIB/ IV lung squamous-cell carcinoma age 70 or older, that had not undergone cytotoxic chemotherapy were enrolled. Patients received docetaxel 25 mg/m2 on days 1, 8, and 15, every 4 weeks. Primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profiles.ResultsA total of 19 patients were enrolled. Among 19 patients, 17 were for evaluated efficacy and safety. In the intent-to-treat population, ORR and disease control rate (DCR) were 11.8% and 47.1%, respectively. In the response evaluable population, ORR was 16.7% and DCR was 66.7%. Median PFS and OS were 3.1 months and 3.3 months, respectively. There were three adverse grade 3/4 events. Grade 1 neutropenia was reported in one patient.ConclusionOur data failed to demonstrate efficacy of a 4-weekly docetaxel regimen, in elderly patients with a poor performance status. However, incidence of side effects, including neutropenia, was lower than with a 3-week docetaxel regimen, as previously reported.

355P - Efficacy and safety of weekly docetaxel regimen for advanced extramammary Paget’s disease: Retrospective single institute analysis

355P - Efficacy and safety of weekly docetaxel regimen for advanced extramammary Paget’s disease: Retrospective single institute analysis

The Role of Immunotherapy and Radiation Therapy in Tumor Chemosensitivity in Advanced Head and Neck Cancer

Patient: Male, 56Final Diagnosis: Advanced stage squamous cell carcinoma of the head and neckSymptoms: Rapidly enlarging mass in left neckMedication: —Clinical Procedure: —Specialty: OncologyObjective:Unusual clinical courseBackground:Cancer is the second leading cause of death internationally, resulting in millions of deaths each year. While treatment in the past has heavily relied on surgery and radiotherapy, chemotherapy and immunotherapy are being increasingly utilized depending on disease presentation.Case Report:A 56-year-old male presented to the Emergency Department with a 3-week history of a rapidly enlarging left supraclavicular neck mass. Computed tomography scan revealed a 12×13 cm mass extending from the angle of the mandible to the supraclavicular area. A biopsy confirmed advanced stage squamous cell carcinoma of the head and neck. The patient was started on a chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TCF). The tumor progressed through chemotherapy, which was switched to cetuximab; however, this therapy was discontinued after an anaphylactic reaction. Palliative radiation treatment was begun along with pembrolizumab. Pembrolizumab was continued, and after 9 cycles, the patient’s cancer was almost in complete remission. Three months later, disease progression was once again noted with pembrolizumab treatment, which was subsequently discontinued. The patient was started on paclitaxel and carboplatin chemotherapy regimen as a last resort, despite failure of prior TCF treatment, and the patient responded, this time with complete remission in 4 months.Conclusions:This case demonstrates a unique outcome in which a patient who previously was resistant to chemotherapy, later responded to chemotherapy after a trial of radiation therapy and immunotherapy. Immunotherapy may have a synergistic effect with radiation therapy and play a role in tumor sensitivity to chemotherapy in head and neck cancer treatment.

PIH13 - ABIRATERONE: A SINGLE-CENTRE EXPERIENCE

Abiraterone is approved for metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed after a docetaxel regimen and those that were on androgen deprivation therapy and not eligible for chemotherapy. This study aims to contribute with real-world data on Abiraterone overall survival (OS) and PSA response between two groups of patients: exposed and not exposed to previous docetaxel chemotherapy. Furthermore, safety profile was also evaluated in both groups. Retrospective cohort chart review study over a 5 year period (January 2013 to January 2018). One hundred and twenty patients were enrolled in the study with a median age of 78 years (range: 48-96). Sixty three patients (52.5%) were not exposed to docetaxel chemotherapy and 47.5% (n=57) were exposed. Comparing the two groups of patients it was observed that those that were not exposed to docetaxel had a significant PSA response rate (63.3% vs 40.0%; p= 0.01). The median overall survival was 29 ± 6.5 [95% CI 16.2-41.8] months for the docetaxel exposed group and 32.5 ± 4.0 [95% CI 24.6-40.4] for the not exposed docetaxel group (log–rank test p value = 0.125). In both groups 80% (n= 96) of patients had documented adverse events, being the most common asthenia 26.7% and peripheral edema 22,5%. Our study indicates that although not reaching statistical significance, those patients that were not exposed to prior docetaxel chemotherapy had an improved overall survival. It was also observed that the PSA response rate was better indicating improved prognosis. The adverse events were not serious or life-threatening. No new safety signals were identified.

Recent updates in perioperative chemotherapy and recurrence pattern of gastric cancer.

Gastrectomy with D2 lymph node dissection has become the global standard procedure for locally advanced gastric cancer to maximally reduce locoregional recurrence. In East Asia, based on the evidence of the ACTS‐GC and the CLASSIC trials, postadjuvant chemotherapy with S‐1 monotherapy or capecitabine and oxaliplatin after curative D2 gastrectomy is the current standard strategy. However, approximately 20% to 30% of patients still develop distant recurrence even after these postadjuvant chemotherapies, especially in those with pathological stage III disease. This review summarizes recent (2008‐2018) evidence on the benefits of adjuvant therapy for locally advanced gastric cancer. JACRO GC‐07, a Phase III trial, recently showed a superior 3‐year recurrence‐free survival of the S‐1 plus docetaxel regimen in comparison to S‐1 monotherapy for patients with pathological stage III gastric cancer after curative D2 gastrectomy. With regard to recent new evidence on neoadjuvant strategy, JCOG0501, a Phase III trial, did not show any superiority in 3‐year overall survival (OS) of additional neoadjuvant chemotherapy with S‐1/cisplatin over postadjuvant S‐1 monotherapy in scirrhous type gastric cancer. Further clinical trials of neoadjuvant chemotherapy are ongoing to improve the poor prognosis for gastric cancer with extensive lymph node metastases. These trials could lead to new evidence for improved treatment of gastric cancer in the near future.

Abstract 3119: Treatment prediction by subset analysis of tumor infiltrating lymphocytes (TILs) in combination therapy with trastuzumab, pertuzumab, and docetaxel for advanced HER2-positive breast cancer

Abstract Background: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. The immune microenvironment in cancer is involved in many antitumor treatment effects, and tumor-infiltrating lymphocytes (TILs) is being established as a biomarker for therapeutic effect and prognosis. Recently, subset analysis of TILs is also under way. We have previously reported the clinical validity and benefits of evaluating TILs for neoadjuvant chemotherapy (NAC). Chemotherapy with a TPD regimen is garnering attention for its clinical outcomes and impact on cancer microenvironments. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators. Methods: The subjects consisted of 30 patients who received the TPD regimen. The expression levels of estrogen receptor (ER), progesterone receptor (PgR), Ki67, CD8, forkhead box protein (FOXP) 3, programmed death (PD) 1, and programmed death ligand (PD-L) 1 were evaluated in biopsy specimens, by immunostaining. We also examined the ratio of CD8 and FOXP3 (CFR). Results: The objective response rate (ORR) in the high CFR group was higher than in the low CFR group (p=0.013). The CD8 positive, high CFR and PD-L1 negative group had significantly longer PFS than the CD8 negative, low CFR and PDL1 positive group (p=0.045, log-rank) (p=0.007, log-rank) (p=0.040, log-rank), respectively. The high CFR group had significantly better OS than the low CFR group (p=0.034, log-rank). Receiver operating characteristic (ROC) analyses showed that, for advanced HER2-positive breast cancer patients, the CFR results [area under the curve (AUC): 0.708] were better than those for the other factors (AUC: CD8=0.681, FOXP3=0.639, PD1=0.528, PD-L1=0.681). Conclusions: This study shows with the TPD regimen, a high CFR leads to a high ORR and long PFS in HER2-positive breast cancer. CFR, therefore, may be one of the important prognostic factors for this disease. Citation Format: Koji Takada, Shinichiro Kashiwagi, Yuka Asano, Goto Wataru, Tamami Morisaki, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Kosei Hirakawa, Masaichi Ohira. Treatment prediction by subset analysis of tumor infiltrating lymphocytes (TILs) in combination therapy with trastuzumab, pertuzumab, and docetaxel for advanced HER2-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3119.

Outcomes of early-stage breast cancer patients treated with sequential anthracyclines–taxanes in relationship to relative dosing intensity: a secondary analysis of a randomized controlled trial

To assess the impact of relative dosing intensity (RDI) on the outcomes of breast cancer patients referred for adjuvant anthracycline-taxane chemotherapy. This is a secondary analysis of the outcomes of patients in the comparator arm of the BCIRG005 study who received adjuvant adriamycin/cyclophosphamide (AC)-docetaxel regimen. Overall survival was assessed according to RDI through Kaplan-Meier analysis. Univariate and multivariate analyses of parameters affecting overall survival were then conducted through Cox regression analysis. Kaplan-Meier analysis of overall survival according to RDI for the AC-docetaxel regimen (< 90 vs. ≥ 90%) was conducted and it showed that RDI < 90% is associated with worse overall survival (P = 0.006). In univariate Cox regression analysis, the following parameters significantly affected overall survival (P < 0.05): age, T stage, lymph node ratio, hormone receptor status, and grade of the disease and RDI for AC-docetaxel regimen. When these factors were included in multivariate analysis, the following factors were associated with worse overall survival: age less than 40years (P < 0.0001), greater T stage (P < 0.0001), greater lymph node ratio (P < 0.0001), negative hormone receptor status (P = 0.001), high grade (P < 0.0001) and RDI ≤ 90% (P = 0.015). Formal interaction testing between RDI and hormone receptor status has a non-significant P value (P = 0.794). Lower RDI for the whole anthracycline-taxane protocol is associated with worse patient survival. Every effort should be exercised to avoid unnecessary dose reductions and/or interruptions among early breast cancer patients receiving adjuvant anthracycline-taxane chemotherapy.

Efficacy and safety of cisplatin and weekly docetaxel in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Background/AimsWe investigated the efficacy and toxicity of a weekly schedule of docetaxel and cisplatin as a first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).MethodsIn this study, 18 patients with previously diagnosed R/M HNSCC were treated with combination chemotherapy of weekly docetaxel 35 mg/m2 (day 1 and 8) and cisplatin 70 mg/m2 (day 1) as first-line chemotherapy, repeated every 3 weeks.ResultsPartial response and stable disease were observed in six patients (33.3%; 95% confidence interval [CI], 11.1% to 55.6%) and six patients (33.3%; 95% CI, 11.1% to 55.6%), respectively. The median overall survival and progression-free survival were 11.26 months (95% CI, 8.87 to 15.83) and 5.68 months (95% CI, 4.80 to 6.51), respectively. The major toxicity was grade 1/2 anemia (50%). Grade 3/4 neutropenia was observed in one patient (5.6%). Among the non-hematologic toxicities, grade 1/2 hepatotoxicity was most common (22.2%), and grade 3/4 infection was observed in one patient (5.6%). There was no treatment-related mortality.ConclusionsFor patients with R/M HNSCC, a cisplatin and weekly docetaxel regimen showed high efficacy with tolerable toxicity as a first-line treatment.

Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling

BackgroundPersistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast cancer (BC) and to test the ability of scalp cooling in prevention.Patients and methodsBC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed.ResultsIn the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m2 presented a significantly higher prevalence of grades 1 PA (33–52%) and 2 PA (5–12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m2 was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36–13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m2, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m2) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse.ConclusionAdjuvant treatment with docetaxel (CD ≥ 400 mmg/m2) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.