Docetaxel/cisplatin/5-fluorouracil Research Articles

Preoperative versus postoperative docetaxel–cisplatin–fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial

Fluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses. Perioperative chemotherapy in locally advanced resectable gastric cancer (RGC) has been reported improving survival by two large randomized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined. We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospective randomized phase III trial, of which we present the 10-year follow-up data. Patients with cT3-4 anyN M0 or anyT cN1-3 M0 gastric carcinoma, staged with endoscopic ultrasound, computed tomography, bone scan, and laparoscopy, were assigned to receive four 21-day/cycles of docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2)/day over days 1-14, either before (arm A) or after (arm B) gastrectomy. Event-free survival was the primary end point, whereas secondary end points included overall survival, toxicity, down-staging, pathological response, quality of life, and feasibility of adjuvant chemotherapy. This trial was activated in November 1999 and closed in November 2005 due to insufficient accrual. Of the 70 enrolled patients, 69 were randomized, 34 to arm A and 35 to arm B. No difference in EFS (2.5 years in both arms) or OS (4.3 versus 3.7 years, in arms A and B, respectively) was found. A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy. A 12% pathological complete response was observed in arm A. Docetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC. The early stopping could mask the real effectiveness of neoadjuvant treatment. However, the complete pathological tumour responses, feasibility, and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting.

Efficacy and tolerability of weekly docetaxel, cisplatin, and 5-fluorouracil for locally advanced or metastatic gastric cancer patients with ECOG performance scores of 1 and 2.

Docetaxel, cisplatin, 5-fluorouracil (DCF) given every three weeks is an effective, but palliative regimen and significantly toxic especially in patients who have a low performance score. Here, we aimed to evaluate the efficacy and tolerability of a weekly formulation of DCF in locally advanced and metastatic gastric cancer patients. 64 gastric cancer patients (13 locally advanced and 51 metastatic) whose ECOG (Eastern Cooperative Oncology Group) performance status (PS) was 1-2 and who were treated with at least two cycles of weekly DCF protocol as first-line treatment were included retrospectively. The weekly DCF protocol included 25mg/m2 docetaxel, 25mg/m2 cisplatin, and 24 hours infusion of 750mg/m2 5-fluorouracil, repeated every week. Disease and patient characteristics, prognostic factors, treatment response, grade 3-4 toxicity related to treatment, progression free survival (PFS) and overall survival (OS) were evaluated. Of the patients, 41 were male and 23 were female; the median age was 63 (29-82) years. Forty-one patients were ECOG-1 and 23 were ECOG-2. Of the total, 81.2% received at least three cycles of chemotherapy. Partial response was observed in 28.1% and stabilization in 29.7%. Overall, the disease was controlled in 57.8% whereas progression was noted in 42.2%. The median time to progression was 4 months (95%CI, 2.8-5.2 months) and median overall survival was 12 months (95%CI, 9.2-14.8 months). The evaluation of patients for grade 3-4 toxicity revealed that 10.9% had anemia, 7.8% had thrombocytopenia and 10.9% had neutropenia. Non-hematologic toxicity included renal toxicity (7.8%) and thrombosis (1.6%). In patients with locally advanced or metastatic gastric cancer who were not candidates for DCF administered every-3-weeks, a weekly formulation of DCF demonstrated modest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment option for such patients.

A pyriform sinus cancer organ preservation strategy comprising induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, followed by potentiated radiotherapy: a multicenter, retrospective study.

No specific study has evaluated the role of neoadjuvant DCF (docetaxel, cisplatin, 5-fluorouracil) followed by radiotherapy in pyriform sinus cancer, which are often included in studies focusing on laryngeal and hypopharyngeal cancer. We assessed the proportion of patients treated sequentially for a pyriform sinus cancer with a preserved larynx. Overall survival, event-free survival (EFS), survival with 'local control', and treatment tolerance were assessed as well. We retrospectively reviewed 88 patients with advanced pyriform sinus squamous cell carcinoma treated with DCF between 2005 and 2010. After induction, radiation could be potentiated with cetuximab or cisplatin. Most patients (82%) had been treated with organ preservation intent. The response rate to DCF was 85%, including 42% with complete response. Primary tumor was operated in 13 patients (eight with total laryngectomy). Radiotherapy had been delivered to 78 (89%) patients (30 with cisplatin, 39 with cetuximab). Potentiation had been achieved as planned in 52 and 79% of patients treated with cisplatin and cetuximab, respectively. Twenty-three local and three neck recurrences were found. Median overall survival was 16.8 months and 38.3% at 3 years. EFS at 3 years was 29.1% with a hazard ratio for partial responders versus nonresponders of 0.18 (P<0.001), and 0.13 (P<0.001) for complete responders versus nonresponders. Thirty-five percent of patients were alive with their larynx preserved at 3 years. This study confirms the efficacy of induction followed by chemoradiation for pyriform sinus cancer and that response to DCF is predictive of EFS.

681P - Comparison the Efficacy of Second Line Eox and Folfiri Regimens in Metastatic Gastric Cancer

ABSTRACT Aim: Gastric cancer is often diagnosed in advanced stage. Palliative chemotherapy or best supportive care is recommended for patients with metastatic gastric patients. In several clinical trials palliative chemotherapy improved overall survival (OS) and disease free survival (DFS), but the survival benefit of second line chemotherapy was demostrated in small cohort studies. The main aim of our study is to compare the efficacy of second line fluorouracil-folinic acid-irinotecan (FOLFIRI) and epirubicin-oxaliplatin-capacitabine (EOX) regimens. Methods: Metastatic gastric cancer patients who progressed after completed modified docetaxel-cisplatin-fluorouracil (DCF) regimens were included. A total 105 patients were included to this study; 55 and 50 patients were treated with EOX and FOLFIRI regimens. The clinicopathological and demographic characteristics of all patients were collected from the medical charts. Kaplan–Meier survival analysis was carried out for DFS and OS. Results: The median follow-up of our study was 15 (4-85) months. In both groups, all of the patient were treated with prior modified DCF. In our study, prior median DCF cycle was 4 (2-6) and 5 (3-8) in EOX and FOLFIRI groups, respectively. Median cycle of chemotherapy was 3 (1-8) and 3.5 (1-6) in EOX and FOLFIRI groups, respectively (P = 0.44). Median DFS was 5.3 months and 6.3 months (P = 0.91) whereas median OS was 6 and 7 months (P = 0.67) in EOX and FOLFIRI groups, respectively. Six months and 1-year DFS rate was 43.4% and 13.7% in EOX regimen; 54.7% and 11.3% in FOLFIRI regimen arms (P = 0.91). Six months and 1-year OS rate was 48.1% and 24.1% in EOX regimen; 53.8% and 29.3% in FOLFIRI regimen arms (P = 0.67). Conclusions: Published trials and meta-analyses showed the efficacy of second-line chemotherapy in the treatment of metastatic gastric cancer, but the optimal treatment regimen was not still known. In our trial both platin based and irinotecan based second line chemotherapies showed similar efficacy in metastatic gastric cancer. Like iriotekan based regimens, oxaliplatin based regimens can be effective in the second line treatment of metastatic gastric cancer patients. Disclosure: All authors have declared no conflicts of interest.

Docetaxel, cisplatin and 5-fluorouracil adjuvant chemotherapy following three-field lymph node dissection for stage II/III N1, 2 esophageal cancer.

To determine the efficacy of postoperative adjuvant chemotherapy with docetaxel + cisplatin + 5-fluorouracil (DCF) in lymph node metastasis-positive esophageal cancer, we retrospectively analyzed 139 patients with stage II/III (non-T4) esophageal cancer with lymph node metastasis (1-6 nodes), who did not receive preoperative treatment and underwent three-field lymph node dissection in the Juntendo University Hospital between December, 2004 and December, 2009. The tumors were histologically diagnossed as squamous cell carcinoma. The patients were divided into two groups, a surgery alone group (S group, 88 patients) and a group that received postoperative DCF therapy (DCF group, 51 patients). The disease-free and overall survival were compared between the groups and a multivariate analysis of prognostic factors was performed. The same analysis was performed for cases classified as N1 and N2, according to the TNM classification. There were no significant differences between the S and DCF groups regarding clinicopathological factors other than intramural metastasis and main tumor location. The presence of intramural metastasis, blood vessel invasion and the number of lymph nodes were identified as prognostic factors. The 5-year disease-free and overall survival were 55.8 and 57.3%, respectively, in the S group and 52.8 and 63.0%, respectively, in the DCF group. These differences were not considered to be statistically significant (P=0.789 and 0.479 for disease-free and overall survival, respectively). Although there were no significant differences in disease-free and overall survival between the S and DCF groups in N1 cases, both disease-free and overall survival were found to be better in the DCF group (54.2 and 61.4%, respectively) compared to the S group (29.6 and 28.8%, respectively) in N2 cases (P=0.029 and 0.020 for disease-free and overall survival, respectively). Therefore, postoperative adjuvant chemotherapy with DCF was shown to improve disease-free and overall survival in moderate lymph node metastasis-positive cases (N2), suggesting that the DCF regimen may be effective as postoperative adjuvant chemotherapy for patients with lymph node metastasis from esophageal cancer.

P-0042 - Efficacy and Safety of Triweekly Docetaxel, Oxaliplatin, Fluorouracil, and Folinic Acid (DOFF) in Patients with Advanced Gastric or Gastroesophageal Adenocarcinoma

Introduction: Docetaxel, cisplatin, fluorouracil (DCF) regimen improved response rate, quality of life and survival for patients with advanced gastric cancer, but is limited by significant toxicity. In attempt to reduce the toxicity of DCF, we evaluated the efficacy and tolerability of docetaxel associated with oxaliplatin and fluorouracil in a triweekly schedule. Methods: Patients with histologically confirmed locally advanced, recurrent or metastatic gastric or esophagogastric adenocarcinoma treated in our center were reviewed. Patients received docetaxel 75 mg/m2, oxaliplatin 100mg/m2 on day 1, and fluorouracil 400mg/m2 in 2 hours intravenous infusions from day 1 to day 5 preceded by Folonic acid 200mg/m2, every 3 weeks. Responses were evaluated every three cycles according to RECIST criteria and toxicities were graded according to NCI-CTC- AE v3 scale. Results: Twenty two patients were included in this study. Median age was 59 years [range: 35-79]. The majority (77.3%) of patients had good (0-1) Performance Status (ECOG scale). Primary tumor location was the stomach in 16 patients (72.7%) and the esophagogastric junction in 6 (27.3%). Disease was locally advanced in 7 patients (31.8%) and metastatic in 15 patients (68.2%). The most common sites of metastasis were lymph nodes (66.6%), liver (46.6%) and peritoneum (40%). Treatment was administrated as first line in 17 patients (77.3%) and second line in 5 patients (22.7%). Median number of cycles received was 6 [range: 2-12]. Grade 3 or 4 hematological toxicities consisted in neutropenia (18.2%) and anemia (4.5%). Febrile neutropenia was observed in two patients (9.1%). Main G3-4 non hematological toxicities were diarrhea (13.6%) and peripheral neuropathy (13.6%). Dose reductions of drugs were required in fifteen patients (68.2%) but there were no treatment-related deaths. Eighteen patients (81.8%) had measurable disease; objective response rate was 50% with a complete response in four patients (22.2%) and partial response in 5 (27.8%). Stable disease was observed in one patient (5.5%). After a median follow-up of 15.2 months, 9 patients (40.9%) had died. Median time to progression was 4.2 months. The disease control rate at 6 months was 36.4%. Tumor downstaging allowed curative surgery in 5 of the seven patients (71.1%) with locally advanced disease initially considered as unresectable. Conclusion: Triweekly Docetaxel, Oxaliplatin, Fluorouracil and Folinic acid (DOFF) has an acceptable safety profile for patients with advanced gastric or esophagogastric cancer and could favor tumor resection in the neoadjuvant setting.

Outcomes of Preoperative Chemotherapy with Docetaxel, Cisplatin, and 5-Fluorouracil Followed by Esophagectomy in Patients with Resectable Node-Positive Esophageal Cancer

There is a consensus that neoadjuvant therapy is an essential component of treatment for resectable advanced esophageal cancer. The aim of this study was to evaluate the efficacy of preoperative docetaxel/cisplatin/5-fluorouracil (DCF) followed by esophagectomy for patients with node-positive esophageal cancer using a prospective database. Fifty-five consecutive patients with resectable node-positive esophageal cancer were treated with preoperative DCF between August 2008 and December 2010. Of these patients, 54 completed 2 courses of DCF, and 50 underwent esophagectomy after the planned chemotherapy. Clinical and pathologic responses to DCF were investigated, as was patient prognosis. Cox proportional hazard regression was used to determine factors that independently affected recurrence. Complete response, partial response, stable disease, and progressive disease were observed in 5, 24, 24, and 2 patients, respectively. Overall, the clinical response rate was 53 %. Pathologic complete response was achieved in 6 cases (12 %), and the overall pathologic response rate was 36 %. Downstaging was observed in 23 cases (46 %). Two-year overall and disease-free survival rates were 78 and 56 %, respectively. Multivariate analysis revealed that residual tumor [R1/2; hazard ratio (HR) 5.21, 95 % confidence interval (CI) 1.64-17.2], pathologic poor response (grade 1a; HR 3.08, 95 % CI 1.08-11.1), and ypN (M1Lym; HR 13.3, 95 % CI 2.06-116) were independent predictors of recurrence. DCF has strong antitumor activity for esophageal cancer and may confer survival benefits when used as preoperative chemotherapy.

術前DCF療法が著効した食道原発内分泌細胞癌の１切除例

Esophageal endocrine cell carcinoma is extremely rare. We report a case of esophageal endocrine cell carcinoma showing histological complete response to neoadjuvant chemotherapy with docetaxel/cisplatin/5-fluorouracil (DCF). A 66-year-old man had been experiencing epigastralgia, and a type 2 tumor in the thoracic part of esophagus was detected by upper endoscopy. The biopsy showed endocrine cell carcinoma. PET/CT, endoscopy and an esophagogram showed that the patient had a 70-mm scaled type 2 tumor in the middle thoracic esophagus, and they also revealed lymph node metastases (no. 106recR). We diagnosed a cT3cN1cM0 cStage III tumor. With two courses of DCF treatment, both the primary tumor and lymph node metastases showed a partial response. We performed a subtotal esophagectomy with three-field lymph node dissection. The pathological examination of the resected specimens revealed no malignant cells in the esophagus or lymph nodes, and we concluded that the pathological effect of the DCF treatment was Grade 3.

Efficacy of Nimotuzumab Combined with Docetaxel–Cisplatin–Fluorouracil Regimen in Treatment of Advanced Oral Carcinoma

The present study aimed to evaluate efficacy and adverse effects of Nimotuzumab combined with docetaxel-cisplatin-fluorouracil regimen in the treatment of advanced oral carcinoma. Nine patients with advanced oral carcinoma were treated with Nimotuzumab combined with docetaxel-cisplatin-fluorouracil regimen (test group). The treatment was given as follows: Nimotuzumab 200 mg, given as intravenous infusion once a week for 6 weeks; docetaxel and cisplatin, 75 mg/m(2) each, on day 1 only; 5-fluorouracil, 750 mg/m(2) infused continually for 8 h, used from day 1 to 5; the total cycle was for 21 days. Another eight patients comprised control group (docetaxel-cisplatin-fluorouracil regimen alone). Study patients from both groups were evaluated for objective response. The response rate was significantly (p = 0.044) higher in test group (88.9 vs. 37.5 % in control group). The disease control rate also tended to be higher in test group (100 vs. 62.5 % in control group; p = 0.083). The major adverse effects were bone marrow suppression, nausea, vomiting, and alopecia. The incidence of adverse effects was similar between both study groups. In conclusion, Nimotuzumab combined with docetaxel-cisplatin-fluorouracil regimen is effective and safe in the treatment of advanced oral carcinoma.

Compliance and efficacy of induction chemotherapy with cisplatin, docetaxel, and fluorouracil followed by radiotherapy plus cisplatin or cetuximab for locally advanced oropharyngeal tumours.

e17012 Background: This study aimed to assess compliance and survival after induction chemotherapy (IC) with docetaxel, cisplatin, fluorouracil (DCF) followed by radiotherapy plus cisplatin (RTCis) or radiotherapy plus cetuximab (RTCet) in a retrospective multicentric series of 121 patients with locally advanced oropharyngeal cancer. One of the issues of these chemotherapy regimens is the toxicity that adversely affects the compliance to the concomitant radiochemotherapy treatment. We also evaluated feasibility and completion of radiochemotherapy treatment comparing efficacy and toxicity between RTCet and RTCis. Methods: Multicentric retrospective review of 121 consecutive patients with non resectable or non operable oropharyngeal carcinomas treated between 2005 and 2011 in 3 tertiary care centers with protocol ongoing in each center. In one center DCF, is followed by RTCet, in the 2 other centers, DCF is followed by RTCis. Primary endpoints were acute toxicity of IC and compliance to the RTCis compared with RTCet. Secondary endpoints were overall survival, disease free survival and locoregional control. Results: Within the 121 patients, 20.7% were stage III and 79.3% were stage IV. 81.8% of the patients completed the full course of IC. 50% of the patients had full dose concomitant cisplatin versus 77% of the patients that had full dose concomitant cetuximab (p=0.017). Mean follow up was 23.5 months. Median overal survival was 20.7 months, median disease free survival was 18.6 months. The 3 and 5 year overall survival rates were respectively 52.5% and 46.4%. The 3 and 5 year disease free survival rates were 44.2% and 38.3%. The only significant factor affecting survival was IC response (p&lt;0.05). No statistically significant difference in survival was found between patients with concomitant cisplatin or cetuximab. Conclusions: Induction chemotherapy with DCF followed by RTCis or RTCet allowed good survival rates with acceptable toxicities. Cetuximab seemed to be better tolerated than cisplatin improving compliance to the treatment.

Early prediction of survival following induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) using FDG PET/CT imaging in patients with locally advanced head and neck squamous cell carcinoma

Locally advanced head and neck squamous cell carcinoma (HNSCC) has a high rate of recurrence. Induction chemotherapy with DCF (docetaxel, cisplatin, 5-fluorouracil) before chemoradiotherapy could lead to the best disease control of inoperable stage III/IV HNSCC but with an increased risk of acute toxicity. Early assessment of therapeutic efficacy is a key issue in considering the benefit of escalation in a poor prognosis population. Patients with stage III/IV HNSCC, in whom DCF induction chemotherapy followed by concurrent chemoradiotherapy had been validated by a multidisciplinary team, were prospectively included in the study. FDG PET/CT scans were performed in all patients before and after two of the three cycles of DCF. EORTC99 criteria were used to evaluate PET responses as follows: group 1 (metabolic responders) showing a complete response (CR) or partial response (PR), and subgroup 0 (metabolic nonresponders) showing stable disease (SD) or progressive disease (PD). The primary endpoint for monitoring patients was event-free survival (EFS). EFS probabilities between the two groups were estimated by the Kaplan-Meier method and statistically compared using the log-rank test. Fifteen consecutive patients (14 men, 1 woman; age 57.5 ± 6.2 years, mean ± SD) were analysed. Therapeutic assessment by PET/CT demonstrated CR in four patients, PR in six, SD in four and PD in one. Among the ten patients with a metabolic response (group 1), none had relapsed at the time of this report, while four of five patients with no metabolic response (group 0) showed recurrence within an average of 9.0 ± 1.6 months. Median EFS was, respectively, 18.9 months (3.8-25.3 months) and 10.2 months (7.5-12.7 months) in group 1 and group 0. The corresponding 1-year EFS rates were 100 % and 20 %, respectively. The difference in EFS between the two groups was statistically significant (p = 0.0014). Early therapeutic response demonstrated on FDG PET/CT after two cycles of induction chemotherapy with DCF in patients with inoperable stage III/IV HNSCC seems to be a predictive factor for EFS.

Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma

Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting.

Abstract 1155: Serum microRNA-21 is a novel biomarker in patients with esophageal squamous cell carcinoma

Abstract Backgrounds and objective: Esophageal squamous cell carcinoma (ESCC) is one of the most difficult malignancies to be cured among gastrointestinal tract cancers. Recently, it was revealed that microRNAs stably exist in serum and may affect pathogenesis of several diseases. However, there are only a few reports that have demonstrated the significance of microRNA (mir) in the serum of patients with ESCC. Accordingly, the aims of this study were to clarify the status of mir-21 in the serum of ESCC patients and to reveal the usefulness of this molecule as a biomarker. Patients and methods: Serum samples were obtained from 52 patients diagnosed with ESCC, as well as from 17 “control” patients diagnosed with gallstones, without active inflammation, in Kumamoto University Hospital from 2008 to 2010. Pre-treatment serum samples were collected during diagnostic studies. Thirty-two ESCC patients received induction chemotherapy using the Docetaxel/ cisplatin /5-Fluorouracil (DCF) regimen (60 mg/m2 Docetaxel on day 1; 350 mg/m2 5-Fluorouracil and 6 mg/m2 cisplatin on days 1-5; 2 courses) after being diagnosed with node-positive ESCC. Twenty-four pairs of serum samples before and after chemotherapy were collected. The expression of miR-21 was determined by qRT-PCR using TaqMan microRNA assay Kits® (Applied Biosystems, USA). Results: The results of qRT-PCR analysis indicated that the ESCC patients had significantly higher levels of serum miR-21 than the control patients (P = 0.007). The value of area under the receiver operating characteristic curve was 0.885 for microRNA-21. When the patients were divided into two groups according to tumor size (≥40mm vs. &amp;lt;40mm), we found that the patient group with the larger tumors exhibited significantly higher levels of miR-21 than the patients with small-sized tumors. We examined the expression levels of miR-21 in the paired (pre- and post-therapy) serum samples of 24 patients who were treated with chemotherapy. The miR-21 expression levels in the patients’ post-chemotherapy samples were significantly reduced compared to the corresponding levels in the pre-chemotherapy samples (P=0.009). When the patient response to cancer chemotherapy was evaluated by RECIST v. 1.0, we found a significant decrease in the miR-21 expression levels in the Complete Response /Partial Response patients, whereas no significant decrease occurred in the levels in Stable Disease/ Progressive Disease patients (P = 0.003 versus N.S). Conclusion:Serum microRNA-21 is considered to be a novel biomarker for diagnosing ESCC, and it can also be used as a response marker during chemotherapy for ESCC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1155. doi:10.1158/1538-7445.AM2011-1155

Progress in chemotherapy for advanced gastric cancer

With the rapid development in cytotoxic agents and molecular targeting drugs, some progress in palliative chemotherapy for advanced gastric cancer has been achieved and the median survival of advanced gastric cancer patients is prolonged to about one year. In this review, we summarized the application of new agents, such as docetaxel, paclitaxel, oxaliplatin, irinotecan, capecitabine, S1 and targeting drugs in the treatment of patients with advanced gastric cancer. We focused on the results of phase III clinical trials and concluded that till now no standard regimens for the treatment of advanced gastric cancer are available. New combination regimens such as docetaxel-cisplatin-fluorouracil (DCF), epirubicin-oxaliplatin-capecitabine (EOX), fluorouracil-leucovorine-oxaliplatin (FLO), irinotecan, leucovorin and 5-FU (ILF), cispaltin plus xeloda, S1 plus cisplatin are considered as new options for the first-line chemotherapy of advanced gastric cancer. Due to uncertain efficacy and safety concerns, the role of molecular targeting agents in the treatment of advanced gastric cancer needs further investigation. It is suggested that neoadjuvant chemotherapy is a suitable choice for locally advanced gastric cancer.

The efficacy and safety of reduced-dose docetaxel, cisplatin, and 5-fluorouracil in the first-line treatment of advanced stage gastric adenocarcinoma

Patients with advanced gastric carcinoma have still had bad prognosis despite advances in the modern treatment era. Docetaxel, cisplatin, 5-fluorouracil (DCF) is effective, but highly toxic regimen for advanced cases. In this study, we modified the standard doses of DCF (mDCF) to evaluate the effectiveness and side effects. From July 2005 to July 2008, 37 advanced gastric cancer patients treated with at least one course of mDCF protocol as first-line treatment were included. The mDCF protocol included 60 mg/m(2) docetaxel and cisplatin for 1 day and 600 mg/m(2)/day, 5-flourouracil infusion for 5 days, repeated every 3 weeks. No patients used prophylactic granulocte -colony stimulating factor. Of the patients, 28 were male and nine were female; the median age was 53 (23-65) years. Of them, 83.8% received at least four courses of chemotherapy and 64.9% completed the preplanned six courses of treatment. Eleven (29.7%) of those patients who received mDCF in the first-line treatment used the FOLFIRI (5-FU, folinic acit, irinotekan) regimen for the second-line treatment. Response rates were evaluated according to RECIST criteria in 30 out of 37 patients. The median follow-up time was 7.1 months. The longest follow-up time was 19.9 months. Two patients (5.4%) had complete response, nine (21.6%) had partial response, and 14 (37.9%) had stabilized disease; overall, the disease was controlled in 25 patients (64.9%) whereas five patients (13.5%) had progression. Median time to progression was 6.7 months and overall survival was 10 months. The assessment of patients for grade 3-4 toxicity revealed that while 5.4% had anemia and 8.1% had neutropenia, 5.4% nausea and 5.4% diarrhea. Neutropenic fever developed in two patients, requiring hospitalization. G-CSF was used in three patients. Two patients with neutropenic fever and two with severe anemia (total number 4; 10.8%) received delayed chemotherapy. Dose reduction was required in four patients (10.8%), one due to neutropenia, one due to nephrotoxicity, and two due to nausea. No patient died due to chemotherapy toxicity. This retrospective study suggested that mDCF might have comparable efficacy with classical DFC, with better toxicity profile. However, its small size and retrospective nature should be considered when interpreting the results.

Treatment of Head and Neck Cancer

To the Editor: In the report by Posner et al. (Oct. 25 issue)1 on the treatment of head and neck cancer, we question the authors’ implication that the 91-11 trial of the Radiation Therapy Oncology Group and Head and Neck Intergroup showed that cisplatin–fluorouracil (PF) induction followed by radiotherapy for laryngeal preservation is equivalent to or better than concomitant cisplatin and radiotherapy. The 91-11 trial was not designed to show equivalence.2 Both combinations resulted in better laryngectomy-free survival than did radiotherapy alone, but the composite end point does not account for a preserved larynx in patients whose death was not due to laryngeal cancer (over half the deaths). Rates of laryngeal preservation and locoregional control provide a much better assessment, and for both end points, the rates were significantly better with concomitant cisplatin and radiotherapy than with radiotherapy alone or PF induction followed by radiotherapy, whereas overall survival did not differ significantly.2,3 The results of the 91-11 trial do not justify the use of docetaxel–cisplatin–fluorouracil (TPF) sequential therapy for T3 and low-volume T4 laryngeal cancer. Arlene Forastiere, M.D.

The role of docetaxel in gastric cancer

Abstract To date, there has been no global standard chemotherapy for advanced gastric cancer and patient outcomes remain poor. This has led to a concerted effort to find more active treatments. Single-agent docetaxel has shown encouraging clinical activity, and Phase II studies have established docetaxel-cisplatin-5-fluorouracil (DCF) as the most promising docetaxel-containing regimen for further evaluation. TAX 325, the largest Phase III trial to date of patients with advanced gastric adenocarcinoma (n = 445), has demonstrated a significant survival advantage, higher overall response rate, improved clinical benefit and better preservation of quality of life for DCF vs. cisplatin-5-fluorouracil (CF) — a previous reference regimen. Although haematological toxicity was higher with DCF, prophylaxis with granulocyte colony-stimulating factor, awareness of the risk of neutropenic complications and early intervention can all help to manage the toxicity. Addition of docetaxel to CF or other active agent(s) represents an important new front-line option for patients with advanced gastric or gastro-oesophageal cancer and should be a new reference regimen for further clinical studies.

Genetic risk assessment and beyond: Anything new?

To date, there has been no global standard chemotherapy for advanced gastric cancer and patient outcomes remain poor. This has led to a concerted effort to find more active treatments. Single-agent docetaxel has shown encouraging clinical activity, and Phase II studies have established docetaxel-cisplatin-5-fluorouracil (DCF) as the most promising docetaxel-containing regimen for further evaluation. TAX 325, the largest Phase III trial to date of patients with advanced gastric adenocarcinoma (n = 445), has demonstrated a significant survival advantage, higher overall response rate, improved clinical benefit and better preservation of quality of life for DCF vs. cisplatin-5-fluorouracil (CF) — a previous reference regimen. Although haematological toxicity was higher with DCF, prophylaxis with granulocyte colony-stimulating factor, awareness of the risk of neutropenic complications and early intervention can all help to manage the toxicity. Addition of docetaxel to CF or other active agent(s) represents an important new front-line option for patients with advanced gastric or gastro-oesophageal cancer and should be a new reference regimen for further clinical studies.