Docetaxel Combination Chemotherapy Research Articles

The efficacy of gemcitabine and docetaxel chemotherapy for the treatment of relapsed and refractory osteosarcoma: A systematic review and pre-clinical study.

Osteosarcoma is the most common primary malignancy of the bone. There is a lack of effective treatments for patients who experience relapsed osteosarcoma. One treatment for relapsed patients is gemcitabine and docetaxel combination chemotherapy (GEMDOX). This systematic review aimed to establish the efficacy of this chemotherapy regimen, as well as identify the common severe toxicities that are associated with it. Resistant osteosarcoma cell lines developed from MG-63 and HOS-143B were used to represent relapsed osteosarcoma patients in a pre-clinical study. We identified 11 retrospective and Phase II studies that were suitable for inclusion in our review. 10.65% of patients had a response to gemcitabine and docetaxel combination therapy and the disease control rate was 35% (n = 197). 36%, 35.3% and 18.04% of patients experienced grade 3 or 4 neutropenia, thrombocytopenia and anaemia respectively (n = 133). Male patients (X2 = 9.14, p < 0.05) and those below the age of 18 (X 2 = 10.94, p < 0.05) responded better to GEMDOX treatment than females and patients older than 18 years. The resistant osteosarcoma cell lines remained sensitive to either single-agent gemcitabine, docetaxel, and the combination of both. Cisplatin-resistant models (MG-63/CISR8 & HOS-143B/CISR8) were the most responsive to GEMDOX treatment compared to doxorubicin, methotrexate, and triple-combination resistant models. GEMDOX treatment has potential efficacy in relapsed osteosarcoma patients especially those with cisplatin resistance. To directly compare the efficacy of GEMDOX therapy against other therapies randomised phase III clinical trials with adequate patient follow up must be performed to improve treatment options for osteosarcoma.

Prognosis of patients with residual pathological disease after neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy and surgery for esophageal squamous cell carcinoma: a retrospective cohort study.

Docetaxel, cisplatin, and 5-fluorouracil (DCF) combination chemotherapy has been established as one of the standard neoadjuvant therapies for locally advanced esophageal squamous cell carcinoma (ESCC). However, little is known about prognostic factors in patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC who are candidates for adjuvant nivolumab. This study aimed to investigate prognostic factors in patients with residual pathological disease after neoadjuvant DCF chemotherapy followed by surgery for locally advanced ESCC. This was a retrospective cohort study. This retrospective cohort study included patients who received neoadjuvant DCF followed by surgery for locally advanced ESCC between June 2014 and January 2020 at the National Cancer Center Hospital East. Among a total of 210 patients, 45 patients (21.4%) achieved a pathological complete response. The 3-year disease-free survival (DFS) rate was significantly lower in patients with residual pathological disease than in those with a pathological complete response [53.5% versus 74.5%; hazard ratio (HR): 2.09, 95% confidence interval (CI): 1.16-3.77, p = 0.01]. In patients with residual pathological disease (n = 165), multivariate analysis revealed that pathological node positivity (HR: 3.59, 95% CI: 1.92-6.71, p < 0.01), supraclavicular lymph node metastasis (HR: 2.15, 95% CI: 1.19-3.90, p = 0.01), and lymphovascular invasion (HR: 1.90, 95% CI: 1.14-3.17, p = 0.02) were significantly associated with poor DFS. In this largest-to-date cohort study, patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC had a poor prognosis. In these patients, pathological node positivity, including supraclavicular lymph node metastasis, and lymphovascular invasion were considered significant prognostic factors.

A randomized phase III study of docetaxel alone versus docetaxel plus S-1 in patients with previously treated non-small cell lung cancer: JMTO LC09-01.

This study evaluated the efficacy and safety of the combination chemotherapy of docetaxel plus S-1 in patients with previously treated non-small cell lung cancer (NSCLC) compared to docetaxel alone. Patients with previously treated NSCLC were randomly assigned to docetaxel alone (arm A) or a combination of docetaxel and S-1 (arm B) for a maximum of four cycles. The primary endpoint was overall survival (OS). The study was terminated early because of poor accrual. The number of patients evaluated were 74 and 77 in arm A and arm B, respectively. The median OS was 9.8 months (95% confidence interval [CI]: 6.8-15.2) and 12.3 months (95% CI: 9.2-14.5) in arms A and B, respectively. In arms A and B, the median progression-free survival was 3.5 months (95% CI: 2.7-4.0) and 4.1 months (95% CI: 3.2-4.7), respectively. No statistically significant difference was observed in OS (hazard ratio [HR]: 0.984, 95% CI: 0.682-1.419, p = 0.4569) or progression-free survival (HR: 0.823, 95% CI: 0.528-1.282, p = 0.0953). The major toxicity was myelosuppression. The incidence of grade 3 or more neutropenia was higher in arm A than in arm B (44.6% vs. 35.1%). However, the incidence of grade 3 or more febrile neutropenia and infection with neutropenia (12.2% vs. 22.1%) was more frequently observed in arm B. The prematurely terminated study did not show the benefit of two cytotoxic agents over single-agent therapy for previously treated NSCLC patients.

Docetaxel in combination with metformin enhances antitumour efficacy in metastatic breast carcinoma models: a promising cancer targeting based on PEGylated liposomes.

Metformin has been shown to kill cancer stem-like cells in genetically various types of breast carcinoma. With the aim to simultaneously eradicate the bulk population of tumour cells and the rare population of cancer stem-like cells in breast cancer tissues, we used the combination chemotherapy of docetaxel (DTX) with metformin (MET). Furthermore, we introduce an active loading method based on ammonium sulphate 250 mM (SA) for encapsulating docetaxel into liposomes. Docetaxel and metformin encapsulated into PEGylated liposomes with two different methods based on remote or passive loading methods, respectively. The size and surface charge of the liposomes were characterized. DTX content in the nanoliposomes was measured by the high-performance liquid chromatography method. The drug release profiles were evaluated in phosphate-buffered dextrose 5% with the pH of 6.5 and 7.4. We examined the antitumour activity of Taxotere (TAX), and liposomal formulation of DTX and MET as a monotherapy or combination therapy. The biodistribution of liposomes was also investigated using 99mTc hexamethyl propylene amine oxime method in BALB/c mice bearing 4T1 breast carcinoma tumours. The final formulations were prepared according to the best physicochemical characteristics which were HSPC/mPEG2000-DSPE/Chol (DTX liposomes) and HSPC/DPPG/mPEG2000-DSPE/Chol (MET liposomes), at molar ratios of 85/5/10 and (55/5/5/35), respectively. In vivo experiments showed that when free or liposomal metformin used in combination with liposomal docetaxel, they prolonged median survival time (MST) from 31 in the control group to 46 days, which demonstrates their promising effects on the survival of the 4T1 breast carcinoma mice models. Moreover, combination therapies could significantly increase life span in comparison with phosphate-buffered saline (PBS) and Taxotere groups at the same dose. Furthermore, in the combination therapy study, treatment with DTX liposomes prepared by ammonium sulphate 250 mM buffer alone resulted in similar therapeutic efficacy to combination therapy. The biodistribution study exhibited significant accumulation of DTX liposomes in the tumours due to the Enhanced Permeability and Retention effect. This study also showed that metformin-based combinatorial chemotherapies have superior efficacy versus their corresponding monotherapy counterparts at same doses. The findings confirm that liposomes based on ammonium sulphate 250 mM could be as a promising formulation for efficient DTX delivering and cancer targeting and therefore merit further investigations.

First-line palliative chemotherapy clinical benefit is a key determinant of survival in metastatic uterine leiomyosarcoma

Aim: To evaluate whether obtaining a clinical benefit with first-line therapy in patients receiving palliative systemic therapy with a diagnosis of metastatic uterine leiomyosarcoma (ULMS) provides a survival benefit and the factors that may predict first-line therapy response.&#x0D; Material and Method: This study was a retrospective observational single-center analysis conducted with patients diagnosed with metastatic ULMS. Patients who received palliative chemotherapy with an ECOG PS of 0 or 1 at the time of diagnosis of metastatic disease were included in the study. Main patient characteristics, first-line palliative treatment responses, progression-free survival, and overall survival (OS) were reviewed retrospectively. Multivariate analyses were performed to determine the independent predictive factors of first-line palliative treatment response and overall survival.&#x0D; Results: Of the 36 patients whose medical records were evaluated retrospectively, 24 patients who were eligible for the study were included in the study. Gemcitabine plus docetaxel combination chemotherapy was the most commonly used treatment protocol (n=12, 50%) for first-line palliative treatment. While a complete response as a first-line treatment response could not be achieved, clinical benefit (partial remission and stable disease) and progressive disease were observed in 15 (62%) and 9 (37.5%) patients, respectively. Binary logistic regression analysis failed to detect any independent predictive factors for the clinical benefit of first-line palliative therapy. Median (OS) was 19.7 (95% CI, 4.1-35.3) months for all patients (N=24). Median OS was 25.6 (95% CI, 21.0-30.2) months and 6.9 (95% CI, 1.7-12.2) months for patients with and without the clinical benefit of first-line palliative chemotherapy (p=0.004). Cox-regression analysis revealed that increasing age at diagnosis of metastatic disease (HR=0.929, 95% CI 0.870-0.992, p=0.027), pulmonary metastasectomy (HR=0.162, 95%CI 0.031-0.863, p=0.033), and presence of first-line palliative chemotherapy clinical benefit (HR=0.195, 95% CI 0.063-0.606, p=0.005) were independent predictive factors for a better OS.&#x0D; Conclusion: In metastatic ULMS, for which the survival benefit is not clear with palliative chemotherapy, prolonged survival can be obtained in patients with clinical benefit with first-line palliative chemotherapy. There is a need for new studies to determine the factors that will predict the clinical benefit of first-line palliative chemotherapy.

Gemcitabine and Docetaxel Combination Chemotherapy Induced Dermatomyositis Associated with Hand-Foot Syndrome

Gemcitabine and Docetaxel Combination Chemotherapy Induced Dermatomyositis Associated with Hand-Foot Syndrome

Long-term outcomes and safety of radical transmediastinal esophagectomy with preoperative docetaxel, cisplatin, and 5-fluorouracil combination chemotherapy for locally advanced squamous cell carcinoma of the thoracic esophagus

BackgroundIt is unknown whether transmediastinal esophagectomy (TME) is an acceptable surgical procedure for locally advanced esophageal squamous cell carcinoma (ESCC). Therefore, we investigated the feasibility of long-term survival after TME with neoadjuvant docetaxel, cisplatin, and 5-fluorouracil combination chemotherapy (DCF therapy).MethodsThis retrospective, observational study included locally advanced resectable ESCC. All patients received two cycles of preoperative DCF therapy (60 mg/m2 of docetaxel and cisplatin on day 1 and 700 mg/m2/day of 5-FU on days 1–5 in each cycle) followed by radical TME. The main outcomes were survival and the rate of adverse events of chemotherapy and surgery.ResultsSixteen patients were included in this study. All patients received two cycles of DCF therapy, followed by surgery. The median follow-up duration of the 16 patients was 35.4 months. The 2-year overall survival (OS) was 93.3% (95% confidence interval [CI], 61.3–99.0), and the 3-year OS was 78.8% (95% CI, 47.3–92.7). The 2-year and 3-year relapse-free survivals were both 73.3% (95% CI, 43.6–89.1). Leukopenia and neutropenia occurred in most patients; however, they were controllable. Fifteen patients completed TME, and one was converted to open transthoracic esophagectomy because of tracheal injury. Three-field dissection was performed for 12 of 16 patients (75%), and R0 resection was achieved in 15 of 16 patients (93.8%). Three cases of grade IIIb chylothorax were observed. There was no mortality in this study.ConclusionCombined neoadjuvant DCF and TME for locally advanced ESCC was safe and less invasive than traditional therapies and had a satisfactory long-term prognosis.

Distichiasis in association with entropion in metastatic HER2‐positive breast cancer treated by pertuzumab, trastuzumab, and docetaxel combination chemotherapy

We report the first case of distichiasis combined with entropion in a HER2-positive metastatic breast cancer patient treated by pertuzumab, trastuzumab, and docetaxel combination therapy. After 7months, she had ocular complaints including pain, irritation, burning, dryness, and redness in her both eyes. Ophthalmologic examination revealed distichiasis and a mild entropion involving her lower eyelids bilaterally. She remained free of symptom and in complete response to maintenance chemotherapy.

A case of gastric cancer with refractory ascites treated successfully by Nivolumab and CART

Abstract Cancerous peritonitis causes refractory ascites and generally resistant to chemotherapy. Herein, we report a case of gastric cancer with refractory ascites treated successfully by Nivolumab and CART. 58-year-old male was admitted to our hospital because of gastric cancer with pyloric stenosis. We performed distal gastrectomy and the final diagnosis was gastric cancer L type 3 pT4a (SE) N3a H0 P1 pStageIV. Postoperatively, he administered S1 + Docetaxel combination chemotherapy, followed by Paclitaxcel + Ramucirumab combined chemotherapy. Ascites was worsened, so he administered Nivolumab cobined with Cell-free and concentrated ascites reinfusion therapy (CART). Five courses of Nivolumab and 8 times of CART were performed, and his symptoms improved. Adverse events of CTCAE Grade 2 or higher were trunk edema (G3), fatigue (G2), and peripheral sensory neuropathy (G2). The median value of ascites collected at CART was 8100 ml. After that, Nivolumab and CART were ended, but new lesions did not appear.

1566P - Retrospective comparative study of the efficacy and safety in docetaxel and ramucirumab combination chemotherapy with or without previous immune checkpoint inhibitor treatment

BackgroundSalvage chemotherapy after immune checkpoint inhibitor (ICI) treatment has been reported to increase the antitumor effect. There are also some reports that activation of vascular endothelial growth factor (VEGF) / its receptor (VEGFR) signal is one of the ICI resistant mechanism, and that combination therapy of VEGF / VEGFR inhibitor and ICI had synergistic effect. In ICI pretreated patients, docetaxel and ramucirumab combination therapy (DOC+RAM) may be more effective. In order to verify this hypothesis, the retrospective observation study was conducted. MethodsFrom June 2013 to July 2018, in 39 patients with advanced / recurrent non-small cell lung cancer who underwent DOC+RAM therapy at our hospital the efficacy and safety were analysed based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. ResultsOf the 39 patients treated with DOC+RAM, 18 (pre-ICI+: 46%) patients had been pretreated with ICI. The characteristics (pre-ICI+/ pre-ICI-) were as follows; median age was 67/65 years, median treatment line was 3/3, ECOG PS:0,1 was 94%/86%, 83%/48% were male, 72%/95% had adenocarcinoma, and 89%/67% were smokers, PD-L1status ≧50% was 6%/5%, 11%/38% had EGFR mutation. The ORRs for DOC+RAM in pre-ICI+ and pre-ICI- were 38.9% vs. 19.0%, respectively (p=0.29). Median progression free survival was 5.7 vs. 2.3 months (hazard ratio (HR), 0.36; 95% confidential interval [CI], 0.16-0.80). Median overall survival was 13.8 vs. 10.5 months (HR, 0.41; 95% [CI], 0.16-1.04). Because of adverse events, nine patients (50%) in pre-ICI+ group and two patients (9.5%) in pre-ICI- group discontinued DOC+RAM therapy. Adverse events such as fever (50%/38%), myalgia (39%/9.5%), arthritis (33%/4.8%), pleural effusion (22%/4.8%) and pneumonitis (17%/4.8%) tended to be more frequent in pre-ICI+ group. There were no grade 5 AEs. ConclusionsIn this study, statistically significant prolongation of PFS, the tendency of tumor regression improvement and OS prolongation achieved by DOC + RAM, and the concern of increased toxicity were shown in pre-ICI+ patients. Legal entity responsible for the studyDaijiro Harada. FundingHas not received any funding. DisclosureD. Harada: Honoraria (self), Research grant / Funding (institution): AstraZeneca K.K.; Research grant / Funding (institution): Novartis International AG; Research grant / Funding (institution): Kissei Pharmaceutical Co., Ltd; Research grant / Funding (institution): Takeda Pharmaceutical Company Limited.; Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Bristol-Myers Squibb Company; Honoraria (self): Kyowa Hakko Kirin Co., Ltd.; Honoraria (self): Eli Lilly and Company Nyse: LLY; Honoraria (self): MSD K.K. ; Honoraria (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self): Nippon Boehringer Ingelheim Co ., Ltd. T. Kozuki: Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant / Funding (institution): AstraZeneca K.K; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan K.K.; Honoraria (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers K.K; Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): MSD K.K; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Kyowa Hakko Kirin Co., Ltd; Honoraria (self): Nippon Beohringer Ingelheim Co., Ltd.; Honoraria (self): Nippon-Kayaku Co.; Research grant / Funding (institution): Merck Serono. N. Nogami: Honoraria (self): Astellas Pharma; Honoraria (self): AstraZeneca; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Eli Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Pfizer. All other authors have declared no conflicts of interest.

Previous Immune Checkpoint Inhibitor Treatment to Increase the Efficacy of Docetaxel and Ramucirumab Combination Chemotherapy.

For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment. From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI- patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients. Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS.

Gemcitabine and docetaxel combination chemotherapy for advanced bone and soft tissue sarcomas: protocol for an open-label, non-randomised, Phase 2 study

BackgroundThe prognosis of patients with metastatic or advanced sarcomas is poor and there are few options for treatment. Several studies have shown that gemcitabine and docetaxel (GD) combination chemotherapy has antitumor activity against various subtypes of sarcoma. Recently, some studies have shown a favourable outcome for GD combination chemotherapy for relapsed high-grade osteosarcoma and spindle cell sarcoma of bone. If the effectiveness of GD is proven, this will result in new treatment options for advanced bone and soft tissue sarcomas (STS). The aim of this prospective Phase 2 study is to evaluate the efficacy and toxicity of the GD combination in patients with advanced bone sarcomas and STS.MethodsThis is a Phase 2, single-arm, open-label study to investigate the efficacy and safety of combination chemotherapy with GD for advanced bone sarcomas and STS and will enrol 20 patients. The patients will receive gemcitabine 900 mg/m2 on Days 1 and 8, and docetaxel 70 mg/m2 on Day 8 in 3-week cycles until disease progression or other evidence of treatment failure. The primary aim of this study is to analyse GD’s effect on progression-free survival (PFS). The secondary objectives are to analyse treatment efficacy and safety in terms of response rate, tumour control rate, overall survival, and adverse event rate. The length of follow-up will be 5 years.DiscussionThis study will evaluate the efficacy and safety of combination therapy with gemcitabine and docetaxel for bone sarcomas and STS. If this combination proves to be acceptable, it could be used for as second, third, or later line therapy for patients with sarcomas (especially bone sarcomas). In the future, the role of various treatments, including GD therapy, will be clarified for specific subtypes of sarcoma.Trial registrationThis study was registered as UMIN000031004 (University Hospital Medical Information Network-Clinical Trial Registry: UMIN-CTR) on 1 March 1 2018 and with the Japan Registry of Clinical Trials (jRCT) as jRCTs051180042 on 30 January 2019. The posted information will be updated as needed to reflect protocol amendments and study progress.

Outcomes of preoperative S-1 and docetaxel combination chemotherapy in patients with locally advanced gastric cancer.

The therapeutic outcomes of stage III gastric cancer patient receiving D2 gastrectomy and adjuvant chemotherapy remain unsatisfactory. To improve the long-term outcomes in this population, the combination of docetaxel and S-1 (DS) therapy can be expected to be a useful regimen as neoadjuvant chemotherapy (NAC). This study aimed to prospectively evaluate the efficacy of NAC-DS for clinical stage III gastric cancer. Between January 2010 and December 2013, 26 patients were enrolled. Patients with clinical stage III gastric cancer received two courses of docetaxel 40mg/m2 on day 1, 15 and S-1 40mg/m2 bid orally on day 1-7, 15-21 every 4 weeks, followed by radical D2 gastrectomy. Short- and long-term outcomes were evaluated. This study was approved by the ethics committee of Yokohama City University, and was registered in the University Hospital Medical Information Network (UMIN) database (ID: 000011521). Of 26 patients, 24 (92.3%) patients completed two courses of NAC. After NAC-DS, Grade 3 neutropenia was observed in 5 (19.2%) patients including one patient with febrile neutropenia, anemia in 1 (3.8%) patient and diarrhea in 1 (3.8%) patient. All patients underwent R0 gastrectomy and pathological response was found in 15 (57.6%) patients. Postoperatively, Clavien-Dindo grade II complication occurred in 8 (30.7%) patients and no mortality was observed. The 5-year overall survival (OS) was 57.7%, median OS was 78.7months and recurrence free survival (RFS) was 49.0%, median RFS was 45.4months with 66.5months median follow-up. Pathological response (HR = 0.091, 95% CI 0.011-0.730, p = 0.016) and > 5% body weight loss before NAC-DS (HR = 0.133, 95% CI 0.023-0.765, p = 0.024) were independent risk factors for recurrence, > 5% body weight loss before NAC-DS (HR = 0.133, 95% CI 0.023-0.765, p = 0.024) were independent risk factors for overall survival by multivariate analysis. NAC-DS demonstrated acceptable toxicity with a high R0 resection rate in clinical stage III gastric cancer patients, especially in patients with good nutritional status. Further prospective study is warranted to compare the long-term outcomes between with and without NAC-DS.

Long-Term Survival for 8 Years of Peritoneal Recurrence of a Gastric Cancer Treated with S-1/docetaxel Combination Chemotherapy

Long-Term Survival for 8 Years of Peritoneal Recurrence of a Gastric Cancer Treated with S-1/docetaxel Combination Chemotherapy

RPN2 is effective biomarker to predict the outcome of combined chemotherapy docetaxel and cisplatin for advanced gastric cancer.

Preoperative chemotherapy, often using docetaxel and cisplatin, is a famous treatment option for advanced gastric cancer in Japan. But, there are no effective biomarkers that predict the therapeutic outcome on gastric cancer. Ribophorin II (RPN2) silencing, which decreases glycosylation of P-glycoprotein (P-gp) and membrane localization, restores the sensitivity to docetaxel and cisplatin. We inquired whether RPN2 expression in advanced gastric cancer biopsy tissues may be a predictive biomarker for docetaxel and cisplatin combination preoperative chemotherapy.We judged RPN2 expression immunohistochemically in upper endoscopic biopsy tissues from 40 advanced gastric cancer patients, who received the combination preoperative chemotherapy of docetaxel and cisplatin and gastrectomy with D2 resection during 2008-2014, and compared clinicopathological effects between RPN2-positive and RPN2-negative groups. We also examined sensitivity of RPN2-knockout gastric cancer cells by genome editing to docetaxel and cisplatin.RPN2 expression was observed in 19 of 40 gastric cancer cases. The RPN2-negative group had better clinicopathological responses to docetaxel and cisplatin combination chemotherapy than the RPN2-positive group, especially, in assessment of the histopathological criteria to preoperative chemotherapy. And RPN2-negative group had a significantly higher overall survival and progression-free survival compared to the RPN2-positive group. We also found RPN2-knockout to change docetaxel and cisplatin sensitivity in vitro.RPN2 expression in upper endoscopic biopsy tissues can be an effective predictive biomarker for the treatment outcome to docetaxel and cisplatin combination preoperative chemotherapy in advanced gastric cancer.

P1.03-037 A Phase II Study of Adjuvant Chemotherapy with Docetaxel plus Nedaplatin for Completely Resected Non-Small Cell Lung Cancer

Nedaplatin, a cisplatin derivative, has similar activity to cisplatin for non-small-cell lung cancer (NSCLC). We previous reported that the combination chemotherapy of docetaxel plus nedaplatin was well tolerated in patients with advanced NSCLC. The purpose of this phase II study was to evaluate the feasibility of combination chemotherapy of docetaxel plus nedaplatin as adjuvant chemotherapy in patients with completely resected stage IB-IIIA NSCLC.

Efficacy and toxicity of docetaxel combination chemotherapy for advanced squamous cell cancer of the head and neck.

The aim of the present study was to evaluate the clinical effectiveness and toxicity of docetaxel with 5-fluorouracil and cisplatin as combination treatment in patients with curable or metastatic/recurrent head and neck cancer by a retrospective cohort study of patients treated at a single institution between 2007 and 2012. Patients with locally advanced, metastatic and/or recurrent squamous cell carcinoma of the head and neck (SCCHN), who were treated with a combination therapy including docetaxel, were considered as eligible. Survival data, clinical side effects, quality of life (QoL) and toxicity profile were retrieved from patient charts, analyzed and scored according to the National Cancer Institute Common Toxicity Criteria, version 4, and the Response Evaluation Criteria In Solid Tumors, version 1.1. An overall response rate of 86% and a 3-year survival of 65.1% were observed. The median progression-free survival was 32 months. The cumulative incidence after 3 years was 16.9% for local recurrence and 10.4% for distant metastasis. Leukopenia (58%) and anemia (51%) were the most common hematological toxicities, followed by hepatotoxicity (53%) and nausea (27%). A total of 31% of the patients experienced a compromise in their QoL following therapy completion. In conclusion, docetaxel in combination with cisplatin and 5-fluorouracil was found to effectively prolong survival in patients with locally advanced and/or recurrent metastatic SCCHN. The overall survival, progression-free survival and response rates were in accordance with those reported by previous clinical trials. Therefore, this therapy protocol is recommended for patients with SCCHN in the curative as well as the palliative settings.

Conversion surgery after combination chemotherapy of docetaxel, cisplatin and S-1 (DCS) for far-advanced gastric cancer.

A triplet regimen of docetaxel, cisplatin, and S-1(DCS) is highly effective against metastatic gastric cancer. We performed this study to clarify the safety and efficacy of surgical resection in patients with initially unresectable gastric cancer, after down-staging or disease control was achieved by DCS chemotherapy. The subjects of this retrospective study were 31 consecutive patients with initially unresectable gastric cancer, who underwent surgical resection between October, 2006 and December, 2012, after down-staging or disease control was achieved by DCS chemotherapy. We evaluated the clinicopathological factors and clinical outcomes and assessed radiographic response based on the RECIST criteria, not by central review. Before DCS chemotherapy, 18 patients had extra-regional lymph node metastasis, 5 had liver metastasis, 8 had macroscopic peritoneal metastasis, and 8 had pancreatic head invasion. Twenty-three (74.2%) of the 31 patients underwent R0 resection. Postoperative morbidity and mortality rates were 16.1 and 0%. During chemotherapy, grade 3/4 toxicities included neutropenia (54.8%), leukopenia (32.3%), and anemia (16.1%). Median progression-free survival and median overall survival (OS) were 42.1 and 56.1 months, respectively. These results were similar for all patients, except those with locally advanced disease alone. In the multivariate analysis for OS, ypN remained an independent negative prognostic factor (p = 0.018). Surgical resection after DCS chemotherapy for initially unresectable gastric cancer was safe and provided a reasonable R0 resection rate and good mid-term survival.

Bilateral blindness with secondary retinitis pigmentosa following postoperative docetaxel and platinum combination chemotherapy in primary small-cell carcinoma of the endometrium: An unusual case report and review of the literature.

Ocular toxicity is an uncommon complication of cytotoxic chemotherapy. Bilateral blindness with secondary retinitis pigmentosa (RP) following docetaxel and platinum combination chemotherapy at the recommended dose is extremely rare. The present study reports a case of advanced small-cell carcinoma (SCC) of the endometrium in a patient with diabetes mellitus type 2. The patient suffered from RP with a sharp decline in vision after the fourth course of postoperative docetaxel and platinum combination chemotherapy. Unfortunately, the patient developed bilateral blindness after another course of chemotherapy at a reduced dose. No tumor recurrence was observed during the 33 months of follow-up. A total of 35 cases of docetaxel- and/or platinum-induced retinal toxicity were found in the English literature and reviewed. The ischemic and electrophysiological hypotheses may have been implicated in the pathogenesis of ocular toxicity in the present case, particularly with the history of diabetes. Understanding the ocular side effects of this combination chemotherapy may assist gynecological oncologists and ophthalmologists with early recognition and timely intervention before blindness is established.

Trastuzumab-Docetaxel Combination Chemotherapy Induced Severe Onychopathy.

Trastuzumab-Docetaxel Combination Chemotherapy Induced Severe Onychopathy.