Definitive chemoradiotherapy with capecitabine and cisplatin for elder patients with locally advanced squamous cell esophageal cancer

Purpose

The aim of this retrospective study is to evaluate the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) or sequential chemoradiotherapy (SCRT) with capecitabine and cisplatin for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

A total of 75 patients elder than 65 years with histologically proven stage II–III ESCC were enrolled, in whom 40 patients were treated with CCRT consisted of two cycles of intravenous cisplatin and oral capecitabine during and after radiotherapy and 35 patients were treated with SCRT as two cycles of capecitabine plus cisplatin before and after radiotherapy. Response rate, overall survival, progression-free survival and toxicity were compared.

Results

The overall response rate (CR + PR) in the CCRT group (91.6 %) was significantly higher than that in the SCRT group (67.7 %), P = 0.023. The median PFS and median OS were significantly higher in CCRT group (19.7 and 33.6 months) than those in SCRT group (11.6 and 15.7 months), P < 0.05. The acute toxic effect was more severe in the CCRT group than in the SCRT group, but the grade 3–4 acute toxicities were similar in two groups.

Conclusions

It suggested that both CCRT and SCRT with capecitabine and cisplatin are tolerable and effective for elderly patients with locally advanced ESCC. Concurrent CRT might be superior to SCRT.     

Survival and prognostic factors of unresectable pancreatic cancer

GOALS: The aim of this study was to evaluate the prognostic significance of clinical and laboratory variables, and to investigate survival benefits for different treatment modalities in unresectable pancreatic cancer. BACKGROUND: The majority of pancreatic cancers are found to be unresectable. Therefore, estimations of prognosis and decisions of treatment modalities are important in optimizing the various aspects of care. STUDY: Three hundred and forty unresectable locally advanced, or metastatic pancreatic cancer patients were enrolled from January 1998 to January 2005 at the Seoul National University Hospital. RESULTS: One hundred and five patients received chemotherapy only and 59 patients received concurrent chemoradiotherapy (CCRT). Age, performance status, tumor location, initial CA 19-9 level, American Joint Committee on Cancer stage, and treatment modality (supportive care only, chemotherapy, vs. CCRT) were found to have prognostic significance for overall survival (OS) by univariate analysis, whereas initial CA 19-9 level, stage, and treatment modality were identified as independent prognostic factors by multivariate analysis. In subgroup analysis, stage III patients treated by CCRT (median OS, 10.4 mo) or chemotherapy alone (11.3 mo) showed survival benefit over supportive care (6.4 mo), and stage IV patients treated by chemotherapy alone (6.4 mo) showed survival benefit over supportive care (3.1 mo). CONCLUSIONS: Initial CA 19-9, American Joint Committee on Cancer stage, and treatment modality were independent prognostic factors of OS, and the patients who received chemotherapy or CCRT showed better survival than those who received supportive care only.     

Adjuvant sunitinib following chemoradiotherapy and surgery for locally advanced esophageal cancer: a phase II trial

The prognosis for locally advanced esophageal cancer is poor despite the use of trimodality therapy. In this phase II study, we report the feasibility, tolerability and efficacy of adjuvant sunitinib. Included were patients with stage IIa, IIB or III cancer of the thoracic esophagus or gastroesophageal junction. Neoadjuvant therapy involved Irinotecan (65 mg/m²) + Cisplatin (30 mg/m²) on weeks 1 and 2, 4 and 5, 7 and 8 with concurrent radiation (50Gy/25 fractions) on weeks 4–8. Sunitinib was commenced 4–13 weeks after surgery and continued for one year. Sixty‐one patients were included in the final analysis, 36 patients commenced adjuvant sunitinib. Fourteen patients discontinued sunitinib due to disease recurrence (39%) within the 12‐month period, 12 (33%) discontinued due to toxicity, and 3 (8%) requested cessation of therapy. In the overall population, median survival was 26 months with a 2 and 3‐year survival rate of 52% and 35%, respectively. The median survival for the 36 patients treated with sunitinib was 35 months and 2‐year survival probability of 68%. In a historical control, a prior phase II study with the same trimodality therapy (n = 43), median survival was 36 months, with a 2‐year survival of 67%. Initiation of adjuvant sunitinib is feasible, but poorly tolerated, with no signal of additional benefit over trimodality therapy for locally advanced esophageal cancer.     

Phase I study of docetaxel, cisplatin and concurrent radiotherapy for locally advanced gastric adenocarcinoma

This phase I study is designed to determine the maximal tolerated dose and the dose-limiting toxicity of docetaxel with cisplatin and concurrent radiotherapy in patients with unresectable locally advanced gastric adenocarcinoma. Docetaxel was given once a week with the dosage escalated from 5 mg/m(2) to 15 mg/m(2) in increments of 2.5 mg/m(2). Cisplatin were administered at 20 mg/m(2) once a week. Radiotherapy was delivered to 50.4Gy at 1.8Gy/day. At least three patients were enrolled at each level. The maximal tolerated dose (MTD) and dose-limiting toxicity (DLTs) was determined. The DLTs were defined as grade 3 or 4 hematologic and nonhematologic toxicity. Twenty-one patients with locally advanced gastric adenocarcinoma were enrolled. Grade 1-2 neutropenia and nausea/vomiting were the most common side effects. The first DLT (grade-3 neutropenia) was observed in one of three patients at 12.5 mg/m(2) docetaxel. Three more patients were enrolled, but DLT was not observed and 6 patients were enrolled into 15 mg/m(2) group, DLT occurred in 3 patients (1 Grade 3 neutropenia, 1 Grade 4 neutropenia and 1 Grade 3 nausea/vomiting). Overall tumor response rate was 66.7% with 28.6% complete and 38.1% partial response. In conclusion, the MTD of docetaxel was 15 mg/m(2), and the recommended dose of docetaxel for Phase II study was 12.5 mg/m(2) weekly. The docetaxel and cisplatin with concurrent radiotherapy were tolerable and feasible in treating locally advanced gastric adenocarcinoma.     

Comparison of the treatment results of involved-field and elective nodal irradiation in locally advanced esophageal cancer

Background

In recent years, concurrent chemoradiotherapy (CCRT) has become a standard treatment modality for patients with locally advanced esophageal cancer. On the other hand, there is no international consensus regarding an accurate definition of the clinical target volume (CTV). This study evaluated the clinical outcomes in patients with locally advanced esophageal cancer treated definitively with either (ENI) elective nodal irradiation or (IFI) involved-field irradiation.

Patients and methods

Retrospective analysis of the treatment results for patients with locally advanced esophageal cancer between 2001.5 and 2013.5 was carried out. The eligible patients had T2-4N0-2M0 biopsy-proven squamous cell carcinoma (SCC) of the esophagus and were treated with a curative aim. Patients treated with surgery or radiotherapy alone were excluded. The gross tumor volume (GTV) was delineated based on the FDG-PET CT scans. Patients treated with ENI received radiotherapy on the supraclavicular or celiac area as the clinical target volume (CTV). For IFI planning, CTV is defined as a 3-cm superoinferior margin and a 1-cm lateral margin from the GTV. The 3-year progression-free survival, overall survival and patterns of the failures were analyzed.

Results

A total of 99 patients who completed CCRT were eligible for the analysis. Of the patients, 50 patients had ENI and 49 patients had IFI. The age, gender and staging were similar in both groups. The median follow-up was 21 months. Both groups showed a similar overall survival (p = 0.293). On the other hand, although not statistically significant, the IFI group showed a tendency for lower 3-year progression-free survival rates, particularly the non-surgery group (25 vs. 46 %, p = 0.075). The cumulative failure rates were significantly lower in the ENI group than in the IFI group. (35 vs. 56 %, p = 0.04).

Conclusions

Definitive CCRT with ENI did not improve the survival and disease control for patients with esophageal SCC. The omission of ENI was associated with a higher failure rate, but it did not affect the survival time. PET-CT-guided involved-field irradiation is a reasonable option for most locally advanced thoracic esophageal cancer but needs caution for patients who will not undergo surgery.

     

Concurrent chemoradiation for patients with squamous cell carcinoma of the cervical esophagus

Little is known concerning the role of concurrent chemoradiation (CCRT) in the management of carcinoma of the cervical esophagus. We retrospectively evaluated our treatment approach for patients with cervical esophageal cancer with special emphasis on CCRT with or without surgery. Medical records of 21 consecutive patients with cervical esophageal carcinoma treated mainly with CCRT (1997-2004) were reviewed, and factors that influenced patient survival were analyzed retrospectively. Nineteen received CCRT with cisplatin/5-fluorouracil and five underwent curative surgery. Two patients who were deemed unfit for CCRT received radiation therapy alone. All had three-dimensional treatment planning (median total dose, 40 Gy with surgery, 64 Gy without surgery). Of the 19 patients who received CCRT, 11 patients including five who underwent curative surgery achieved initial local control. Neither of the two patients who received radiation therapy alone achieved local control. Among 19 patients who underwent CCRT, 9/11 with T1-3 grade tumors achieved initial local control, but only 2/8 patients with T4 tumors (P = 0.011, chi(2) test) achieved initial local control. No patient without initial local control survived > 20 months compared with 2-year and 5-year survival rates of 60% and 40% in those who achieved initial local control (P = 0.038). No patient with T4 tumors survived > 18 months, whereas 2- and 5-year survival rates were 62% and 41%, respectively, in those with T1-3 tumors (P = 0.006). The significant effect of T-classification on survival was maintained when analyzed among 19 patients who received CCRT. CCRT shows promise for cervical esophageal carcinoma. T-classification and initial local control had significant impact on survival.     

Efficacy and toxicity of fluorouracil, doxorubicin, and cisplatin/nedaplatin treatment as neoadjuvant chemotherapy for advanced esophageal carcinoma

OBJECTIVE: Patients with advanced esophageal carcinoma including clinical T4 tumor, extensive lymph node metastasis, or intramural metastasis have a dismal prognosis, despite recent multimodality treatments. The aim of this study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy using fluorouracil, doxorubicin, and cisplatin or nedaplatin (FAP/N) in these patients. MATERIAL AND METHODS: Twenty-six patients were enrolled in this study. The first 9 patients received 600 mg/m2 fluorouracil on days 1-7 and days 29-35, and 30 mg/m2 doxorubicin and 60 mg/m2 cisplatin on days 1 and 29 (FAP). The next 17 patients received modified FAP, in which 50 mg/m2 nedaplatin was given instead of cisplatin (FAN). RESULTS: Grade 3 or 4 toxicities developed in 6 patients (23.1%) during chemotherapy, but there was no discontinuation of treatment. The clinical response rate was 46.2%. Twenty-one patients (80.8%) underwent esophagectomy, and R0 resection was achieved in 16 patients (61.5%). The 1-year survival rates of 26 patients, 21 patients with resectable tumor, 16 with R0 resection, and 12 clinical responders, were 31.3%, 32.1%, 33.3%, and 45.5%, respectively, each with a median survival time of 9 months. The median progression-free survival time of 26 patients was 6 months; in 16 patients with R0 resection progression-free survival was 6.5 months. There was no correlation between the recurrence pattern and tumor spread before treatment. CONCLUSIONS: FAP/N was found to have acceptable toxicities and the ability to control locoregional tumors, but made little contribution to patient survival. The efficacy of this treatment for patients with advanced esophageal carcinoma, however, may not yet be apparent.     

Effects of neoadjuvant radiochemotherapy on pathological staging and prognosis for locally advanced esophageal squamous cell carcinoma

The role of neoadjuvant therapy in the treatment of locally advanced esophageal carcinoma still remains controversial. The aim of this study was to evaluate the effects of neoadjuvant radiochemotherapy on pathological staging and prognosis in the patients with locally advanced esophageal squamous cell carcinoma. Between January 1991 and December 2000, 473 patients with advanced esophageal carcinoma diagnosed by endoscopic biopsy underwent surgical resection in our center. With informed consent, they were randomized into four groups: neoadjuvant chemotherapy, neoadjuvant radiotherapy, neoadjuvant radiochemotherapy, and surgery alone (control group). The preoperative computed tomography staging criteria were the following: Stage I, the tumor limited to the esophageal lumen or the thickness of the esophageal wall varied between 3–5 mm; Stage II, the thickness exceeds 5 mm but no invasion to the mediastinum or distant metastasis; Stage III, the tumor invades adjacent mediastinal structure; and Stage IV, there is distant metastasis. The tumor resection rate, pathological stage, treatment‐related complication, and survival among groups were compared. The radical resection rate for the patients in radiotherapy and radiochemotherapy groups was increased in comparison with the control group (P < 0.05). Their pathological stage after esophagectomy was regressed significantly than that of the control group (50.85%, 55.08% vs. 0%, P < 0.05). The adjuvant chemotherapy group did show significant improvement on resection rate and pathological staging compared with the control group. The treatment‐related complication in the three neoadjuvant groups had no significant difference from that of the control group (P > 0.05). The 3‐year survival rate of radiotherapy and radiochemotherapy groups were significantly higher than that of the control group (69.49%, 73.73% vs. 53.38%, P < 0.05). The 5‐year survival rate of radiochemotherapy group was higher than that of the radiotherapy group although did not show a statistical difference (P > 0.05). Rational application of neoadjuvant radiochemotherapy seems to provide a modest benefit in radical resection and survival in patients with locally advanced esophageal carcinoma.     

Long-term survivors of advanced esophageal cancer without surgical treatment: a multicenter questionnaire survey in Kyushu, Japan

Since the introduction of recent improvements in adjuvant therapy for esophageal cancer, some patients have demonstrated good prognosis. In the present study, we analyzed 3- and 5-year survivors of advanced esophageal cancer who did not undergo any surgical treatment. Between 1990 and 1998, 831 patients were admitted to 14 university hospitals and one cancer center associated with the membership of the Kyushu study group for adjuvant therapy of esophageal cancer. Twelve (1.4%) of the patients were 3-year survivors and 13 (1.6%) were 5-year survivors. The reasons for non-operation were refusal (eight patients), tumor-related factors (11 patients), and host-related factors (six patients). With a single exception, all patients had locally advanced tumors. Almost all long-term survivors had fewer than five lymph node metastases, in regions limited to the neck and/or mediastinum. Radiation therapy was combined with chemotherapy for 16 of the 25 patients, and chemotherapy-based cisplatin was used for 15 of these 16 patients. Fifteen of the patients remain alive; 10 died seven of them from esophageal cancer. Chemoradiation therapy was effective for some patients with locally advanced esophageal cancer, particularly in the absence of or with few lymph node metastases. To improve the prognosis of patients with advanced esophageal cancer who, for various causes, cannot undergo surgical treatment, a new protocol for adjuvant therapy is required.     

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

AIM：To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS： We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS： Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION： Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.     

Randomized trial of 5-fluorouracil, leucovorin and cisplatin in advanced pancreatic cancer.

BACKGROUND/AIMS: Phase II trials of combined 5 fluorouracil, leucovorin and cisplatin have demonstrated an 18-28% response rate in advanced pancreatic carcinomas. We investigated the effect of this chemotherapy regime on patients' survival. METHODOLOGY: Patients included gave informed consent. They had an advanced and proven pancreatic adenocarcinoma. The trial was multicentric, prospective and randomized. It compared a 5-day course of leucovorin (200 mg/m2/day), 5-fluorouracil (375 mg/m2/day) and cisplatin (15 mg/m2/day) repeated every 21 days (23 patients) with a control group (22 patients). The main end points were survival time (Kaplan-Meier and log-rank methods) a[not readable: see text]side effects of chemotherapy. RESULTS: Association of leucovorin, 5-fluorouracil and cisplatin failed to demonstrate any advantage of this regimen compared with supported care alone. Median survival times were 8.6 months (SD +/- 1.8) and 7.0 months (SD +/- 0.6), respectively. The modulation of 5-fluorouracil by leucovorin and cisplatin was well tolerated with moderate toxic effects. CONCLUSIONS: This multicentric trial failed to demonstrate any advantage of the evaluated chemotherapy regime in the palliative treatment of cancer of the exocrine pancreas. Other trials including gemcitabine and/or radiotherapy are needed in advanced pancreatic adenocarcinoma.     

Long term complications and prognostic factors in locally advanced nasopharyngeal carcinoma treated with docetaxel,cisplatin, 5-fluorouracil induction chemotherapy followed by concurrent chemoradiotherapy: A retrospective cohort study

This study was conducted to evaluate the long term complications and their risk factors including of survival outcomes in patients with locally advanced nasopharyngeal cancer (NPC) treated with docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CCRT).Among the patients who were diagnosed as NPC, we consecutively evaluated the late complications in 104 patients who completed 3 cycles of TPF induction chemotherapy followed by CCRT and received regular follow-up by otolaryngologist and oncologist. The prognostic factors for overall survival, relapse free survival and each complication were analyzed based on clinical characteristics.Over a median follow-up of 54 months (range, 7.9–152.9 months), 5-year overall survival rate was 87% for stage II, 89% for stage III, 87% for stage IV patients. The significant prognostic factor for survival is complete response rate after CCRT in multivariate analysis. The most frequent toxicity was ear complication (29.8%) including of hearing loss requiring hearing aid (6.7%) and bone necrosis (3.8%). Decreased renal function over grade 2 was occurred in only 4 patients (3.8%) regardless of the cumulative dose of cisplatin. The long term complications did not affect the survival outcome. Patients who received radiation therapy more than 5400 cGy had better survival outcome than those who did not. However, ear complication was significantly related to radiation dose (≥ 6,600 cGy) and type of radiation therapy (conventional). Age over 65 years was a significant risk factor for both ear and renal toxicity. In conclusion, close follow-up to monitor long-term complications should be performed in patients treated with TPF induction chemotherapy followed by CCRT treatment, especially in elderly patients. Reestablishing the optimal chemotherapeutic agent during CCRT and adjustment of radiation dose after induction chemotherapy could be helpful to reduce the toxicity associated with the subsequent treatment strategy for locally advance NPC patients.     

Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

AIM To clarify the role of neoadjuvant concurrent chemoradiotherapy(NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma(CCA).METHODS We retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows:(1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or(2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging. RESULTS The median disease-free survival(DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were26.0 and 15.1 mo, respectively(P = 0.91). The median overall survival(OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively(P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis(P = 0.01). CONCLUSION NACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.     

Salvage esophagectomy after exclusive chemoradiotherapy: results at the Brazilian National Cancer Institute (INCA)

Surgical resection is considered the gold standard treatment for esophageal cancer, with global cure rates ranging from 15 to 40%. Exclusive chemoradiotherapy has been used for patients with locally advanced esophageal carcinoma or without clinical conditions for esophagectomy, reaching a 5‐year survival rate of up to 30%. However, locoregional control is poor, with local recurrence of 40–60%, being reported in the literature. Maybe, these patients can benefit from salvage surgery. In this study, 15 patients with esophageal cancer submitted to salvage esophagectomy after exclusive chemoradiotherapy treatment were retrospectively analyzed. Salvage esophagectomy was demonstrated to be technically feasible. However, it presents with high surgical morbidity. Currently, salvage esophagectomy is considered the best available treatment to attempt cure in cases of tumor recurrence or persistence after exclusive chemoradiotherapy. All the other types of treatments are regarded as palliative with discouraging survival results.     

Aortic Pseudoaneurysm Formation Following Concurrent Chemoradiotherapy And Metallic Stent Insertion in a Patient With Esophageal Cancer

Aortic pseudoaneurysm formation subsequent to concurrent chemoradiotherapy (CCRT) for esophageal cancer patient with esophageal metallic stent insertion is a rare condition.A 52-year-old man with esophageal cancer, cT4N1M0, stage IIIC, was treated with concurrent weekly cisplatin (30 mg/m²) and 5-Fluorouracil (500 mg/m²) as well as radiotherapy (50.4 Gy in 28 fractions) for 6 weeks. An esophageal metallic stent was inserted for dysphagia 1 week after initiation of CCRT. During the treatment regimen, the platelet count dropped to less than 200 × 10³ /μL. One month after the completion of CCRT, chest CT revealed the presence of an aortic pseudoaneurysm as well as aortoesophageal fistulas. A thoracic aortic endografting was performed and the patient responded well to surgery. However, the patient died 2 months later due to a nosocomial infection.Multimodality treatment for esophageal cancer comprising cisplatin-based CCRT and esophageal metallic stent placement near a great vessel may increase the risk of pseudoaneurysm formation.     

Long-term efficacy of perioperative chemoradiotherapy on esophageal squamous cell carcinoma

AIM: To investigate the role of perioperative chemoradiotherapy (CRT) in the treatment of locally advanced thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Using preoperative computed tomography (CT)-based staging criteria, 238 patients with ESCC (stage ⅡⅢ ) were enrolled in this prospective study between January 1997 and June 2004. With informed consent, patients were randomized into 3 groups: preoperative CRT (80 cases), postoperative CRT (78 cases) and surgery alone (S) (80 cases). The 1-, 3-...     

Tumor length assessed by miniprobe endosonography can predict the survival of the advanced esophageal squamous cell carcinoma with stricture receiving concurrent chemoradiation

There were tumor strictures commonly encountered in the esophageal squamous cell carcinoma (ESCC) to limit the conventional echoendoscope for exact tumor staging and size measurements. This study evaluated the role of miniprobe endosonography (EUS) to predict the survival of ESCC patients after concurrent chemoradiation therapy (CCRT). This study prospectively enrolled ESCC patients to receive high‐frequency miniprobe EUS for the assessments of the tumor size and tumor–node–metastasis (TNM) stage. For the patients defined with advanced stages to receive CCRT as initial therapy, the tumor size parameters assessed by EUS were analyzed for their correlation with the treatment response and the patients' survivals. Fifty‐four patients, >96% with advanced TNM stage III or IV, were enrolled with a medium follow‐up of 320.5 days. Almost all of the 54 cases had partial or complete stricture of the esophageal lumens due to the tumor obstructions at enrollment. The overall median survival was 18.6 months, and the 1‐ and the 2‐year survival rates were 64.9 and 45.2%, respectively. Patients with initial tumor length <6 cm assessed by the pre‐CCRT EUS had a better survival than those with length ≥6 cm (median survival: >56.5 months vs. 11.5 months, P= 0.006). The patients with initial tumor length <6 cm had a higher rate of downstage than those with tumor length ≥6 cm after the first course of CCRT (80.0% vs. 16.7%, P= 0.035). Multivariate Cox regression confirmed the initial tumor length (hazard ratio [HR]= 1.21, P= 0.034) as well as the presence of distal metastasis are both independent predictors of the survival in ESCC patients receiving CCRT. For the ESCC patients, commonly with tumor stricture, the miniprobe EUS to assess tumor length before CCRT can predict the treatment response and the survivals.     

Weekly docetaxel and gemcitabine in previously treated metastatic esophageal squamous cell carcinoma

AIM: To assess the efficacy and safety of weekly docetaxel plus a fixed-dose rate(FDR) of gemcitabine in metastatic esophageal squamous cell carcinoma(SCC).METHODS: A multi-center, open-label, prospective phase Ⅱ study was designed.Thirty-three esophageal SCC patients with documented progression after fluoropyrimidine/platinum-based first-line chemotherapy were enrolled and treated with docetaxel 35 mg/m2 and gemcitabine 1000 mg/m2 iv at a FDR(10 mg/m2 per minute) on days 1 and 8.Treatment was repeatedevery twenty-one days until disease progression, unacceptable toxicity, or consent withdrawal.The primary endpoint was response rate(RR), and secondary endpoints were safety, progression-free survival(PFS) and overall survival(OS).RESULTS: Combination of weekly docetaxel and FDR gemcitabine was well tolerated: the most common treatment-related adverse events were anemia(97%), fatigue(64%) and neutropenia(55%).One patient with multiple lung and lymph node metastases died of respiratory failure after receiving four cycles of chemotherapy, and the possibility of drug-induced pneumonitis could not be completely excluded.Disease control(objective response plus stable disease) in the ITT population was achieved in 88% of patients, and the overall RR was 30%(95%CI: 15%-46%).The median PFS and OS were 4.0(95%CI: 3.4-4.6) and 8.8 mo(95%CI: 7.8-9.8 mo), respectively.CONCLUSION: A combination of weekly docetaxel and FDR gemcitabine showed promising antitumor activity and tolerability in previously treated, metastatic esophageal SCC.     

Concurrent chemoradiotherapy with S‐1 and cisplatin in advanced esophageal cancer

How best to manage advanced esophageal cancer remains unresolved, especially in palliative care. Here, in a pilot study, we evaluated the efficacy and safety of concurrent chemoradiotherapy with S‐1 and cisplatin in advanced esophageal cancer. Patients with locally advanced or metastatic squamous cell carcinoma of the esophagus received S‐1 and cisplatin at doses of 70 mg/m²/day for 14 days and 70 mg/m² on day 1, respectively, every 3 weeks. Concurrently, radiotherapy was started at a dose of 200 cGy/day, up to a total of 5400 cGy. After concurrent chemoradiotherapy, additive chemotherapy was repeated up to six cycles. Thirty patients were enrolled in this study; of the 27 in whom efficacy could be evaluated, an objective response rate was seen in 20 (74.1%), including five (18.5%) complete pathologic responses in primary lesions. Improvement of dysphagia was seen in 21 (76%) patients. In patients with stage II or III esophageal cancer, the median progression‐free survival and overall survival were 10.6 ± 0.6 months (95% CI: 9.4–11.8) and 23.0 ± 5.1 months (95% CI: 13.0–32.9), respectively. In patients with stage IV esophageal cancer, the median progression‐free survival and overall survival were 5.4 ± 1.6 months (95% CI: 2.2–8.6) and 11.6 ± 1.6 months (95% CI: 8.4–14.8), respectively. The main hematological toxicity was neutropenia, but no neutropenic fever was observed. The major non‐hematological toxicities were asthenia and vomiting, mostly of grades 1 and 2. Thus, concurrent chemoradiotherapy with S‐1 and cisplatin may be a promising nonsurgical treatment in advanced esophageal cancer.     

Phase II study of cisplatin combined with weekly gemcitabine in the treatment of patients with metastatic pancreatic carcinoma.

BACKGROUND/AIMS: Combination therapy of gemcitabine and cisplatin has been reported as an effective regimen for advanced pancreatic cancer. However, the toxicity and synergism are known to depend on the schedule of cisplatin. A phase II study was undertaken to determine the efficacy of a single dose of cisplatin in combination with weekly gemcitabine in patients with metastatic pancreatic carcinoma. METHODS: Patients with measurable, metastatic pancreatic carcinoma, not locally advanced diseases, were included. The patients were treated with a combination of gemcitabine 1,000 mg/m(2) i.v. over 30 min administered on days 1, 8, and 15 of each cycle and cisplatin 75 mg/m(2) i.v. administered 6 h after gemcitabine infusion on day 1 with adequate prehydration. Response and toxicity were assessed according to World Health Organization criteria. RESULTS: A total of 52 patients, 5 with recurrent disease after curative operation, were enrolled from January 2000 to March 2004. The objective response rate was 16 of 52 patients (1 complete response and 15 partial response). Disease stabilization was seen in 10 patients (20.8%). The median survival was 11.8 months (95% CI, 10.7-13.0 months), with 76.1% of patients alive at 6 months and 50% alive at 12 months. The median time to progression was 6.1 months (95% CI, 4.16-7.98 months). Major toxicity profiles were thrombocytopenia and neutropenia. CONCLUSIONS: The modified regimen of a single dose of cisplatin per cycle in combination with weekly gemcitabine appeared to have a more favorable therapeutic index and comparable toxicity profiles.