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Background: Distant metastasis is a poor prognostic factor in recurrent/metastatic squamous cell carcinoma of the head and neck. However, limited information on the prognostic impact of locoregional disease is available, despite its life-threatening features. We investigated the prognostic impact of incurable locoregional disease and distant metastasis in recurrent/metastatic squamous cell carcinoma of the head and neck., Methods: We retrospectively analyzed 156 patients with recurrent/metastatic squamous cell carcinoma of the head and neck who received palliative chemotherapy between August 2006 and December 2019., Results: The median follow-up time for all censored patients was 12.1 (range 1.9-63.5) months. The median overall survival was 12.4 (95% confidence interval 10.1-15.1) months. Incurable locoregional disease (hazard ratio: 2.31, P = 0.007), liver metastasis (hazard ratio: 2.84, P = 0.006), disease-free interval > 13 months (hazard ratio: 0.51, P = 0.041), cetuximab use (hazard ratio: 0.59, P = 0.007), and immune checkpoint inhibitor use (hazard ratio: 0.56, P = 0.006) were associated with prognosis. The number of distant metastatic sites was not associated with overall survival (1-2: hazard ratio: 0.60, P = 0.16; 3-4: hazard ratio: 1.34, P = 0.50). Patients with incurable locoregional disease had more life-threatening events than those with curable locoregional disease., Conclusion: The presence of incurable locoregional disease had a significant prognostic impact, whereas the number of distant metastatic sites had no prognostic impact. Liver metastasis was a poor prognostic factor for recurrent/metastatic squamous cell carcinoma of the head and neck., (© 2021. Japan Society of Clinical Oncology.)

Background: De-escalating treatments have been focused on for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). We assessed the efficacy of a triplet induction chemotherapy (ICT) followed by surgery with or without neck dissection (ND) for locally advanced OPSCC, aiming at less invasive surgery without free-flap reconstruction and avoiding postoperative irradiation., Methods: This was a retrospective study of 41 patients with advanced resectable HPV-positive OPSCC who underwent ICT followed by surgery of primary resection with or without ND. Patients underwent triplet ICT, including docetaxel, cisplatin, and 5-fluorouracil, or carboplatin, paclitaxel, and cetuximab., Results: Twenty-nine patients had tonsillar cancer, 15 patients were current smokers, and 18 and 12 patients had T2N1M0 and T1N1M0 status (UICC 8th), respectively. After ICT, a surgical procedure without free-flap reconstruction and tracheostomy was possible in 90.2%. Pathological complete response at both the primary site and lymph nodes was achieved in 73.2%. Of the patients who underwent surgery, no adjuvant radiotherapy was required in 85.0%. Two patients (4.9%) experienced recurrence at regional lymph nodes, but were cured by salvage ND followed by adjuvant radiotherapy., Conclusions: Upfront ICT using highly responsive triplet chemotherapeutic regimens may enable us to perform less invasive surgery without free-flap reconstruction and to avoid postoperative irradiation to the locoregional field through excellent postoperative pathological features.

Background: Docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy (ICT) is a treatment option for locally advanced unresectable head and neck squamous cell carcinoma (LA-HNSCC). However, patients with advanced age, or renal, cardiac or neurogenic dysfunction are ineligible for ICT-TPF., Methods: We retrospectively assessed 24 unresectable LA-HNSCC patients who received paclitaxel, carboplatin and cetuximab (PCE) as ICT at the Shizuoka Cancer Center between April 2013 and October 2018., Results: Patient characteristics were as follows: median age, 72 years (range 60-81); 0, 1, and 2 performance status (PS), 1, 15, and 8 patients, respectively, and creatinine clearance ≥ 60 mL/min or < 60 mL/min, 8 and 16 patients, respectively. The main reasons for PCE selection were renal impairment, older age, cardiac dysfunction, poor PS, and cerebral infarction. Twenty-two patients (92%) completed two or three cycles of ICT-PCE. After ICT-PCE, one patient (4%) and 20 patients (83%) achieved a complete response and partial response, respectively. Twenty-one patients (87%) advanced to definitive locoregional treatment. Median observation period was 25.2 months. The 12-month progression-free and overall survival rates were 75 and 92%, respectively. Median progression-free survival and overall survival were 29.4 and 34.8 months, respectively. Grade 3 or 4 toxicities included neutropenia (58%), oral mucositis (8%), and febrile neutropenia (4%)., Conclusions: ICT-PCE may be a tolerable and potential option for unresectable LA-HNSCC patients ineligible for TPF.

Background: Definitive radiotherapy (RT) for stage II laryngeal cancer is known to be less effective for locoregional control and survival (LRCS) in patients with high-risk factors (e.g., subglottic extension, impaired cord mobility, or bulky tumor size) than in low-risk patients. The purpose of this study was to evaluate the safety and efficacy of chemoradiotherapy (CRT) for stage II laryngeal cancer patients with high-risk factors METHODS: Sixty-five consecutive patients with stage II laryngeal cancer who received radiotherapy (RT) alone or CRT were retrospectively analyzed. The patients were classified into three groups: RT, low risk (RT-low, n = 26); RT, high risk (RT-high, n = 25); and CRT, high risk (CRT-high, n = 14)., Results: The glottis was the most common primary tumor site in all groups. Most patients in the CRT-high group received platinum-based CRT. The 5-year locoregional control and survival (LRCS) rates were 88.3, 44.2, and 85.7% in the RT-low, RT-high, and CRT-high groups, respectively. In multivariate analysis, high-risk disease and CRT were significantly associated with 5-year LRCS rates., Conclusion: CRT may provide better locoregional control than RT alone in high-risk stage II laryngeal cancer.

Background: Prophylactic percutaneous endoscopic gastrostomy (PEG) has been widely performed before concurrent chemoradiotherapy (CCRT) for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) because severe oral mucositis and dysphagia induced by CCRT lead to difficulty with oral intake. However, it is controversial whether all patients require prophylactic PEG for adjuvant CCRT. This study evaluated predictive factors for the feasibility of oral intake in adjuvant CCRT for patients with LASCCHN., Methods: This study retrospectively analyzed 117 LASCCHN patients who underwent surgery followed by adjuvant CCRT with cisplatin at Shizuoka Cancer Center between April 2008 and December 2018. To investigate predictive factors for the feasibility of oral intake, tumor factors, treatment factors and social factors were included in multivariate analyses., Results: Of the 117 patients, 25 received total laryngectomy and 92 received other surgery. In multivariate analysis, total laryngectomy [HR (hazard ratio) 0.09, P = 0.001] and oral cavity of primary tumor location (HR 0.21, P = 0.031) were significantly associated with the feasibility of oral intake. Difficulty obtaining adequate nutrition via oral intake from initiation of CCRT until 1 year after its completion was significantly rarer in the total laryngectomy group than in the other surgery group (16% vs. 57%, P < 0.001)., Conclusion: Our study suggests that majority of patients who underwent total laryngectomy are able to maintain oral intake during adjuvant chemoradiotherapy.

Background: Locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is usually treated with cisplatin (CDDP)-based chemoradiotherapy, except when patients are elderly or have renal, cardiac, or neurogenic dysfunction. This study compared the safety and efficacy of concurrent carboplatin (CBDCA) to cetuximab (Cmab) plus radiotherapy (RT) in patients ineligible for CDDP treatment., Methods: We retrospectively analyzed LASCCHN patients who received CBDCA plus RT (n = 29) or Cmab plus RT (n = 18) due to ineligibility for CDDP treatment at two Japanese institutions between August 2006 and December 2015., Results: Patients characteristics for CBDCA plus RT and Cmab plus RT were: median age, 74 and 75 years; 0-1 performance status, 90% and 100%; main primary tumor site, hypopharynx 52% (n = 15) and oropharynx 39% (n = 7); and stage IV, 90% (n = 26) and 50% (n = 9), respectively. With a median follow-up time of 60.0 months for CBDCA plus RT and 53.6 months for Cmab plus RT, 3-year locoregional control rates were 56% versus 58%, and median progression-free survival was 42.7 versus 11.6 months. CBDCA plus RT was associated with more grade 3/4 hematologic toxicities, including neutropenia and thrombocytopenia, whereas Cmab plus RT was associated with more grade 3/4 oral mucositis and radiation dermatitis., Conclusions: CBDCA or Cmab as a concurrent systemic therapy with RT is a possible treatment option for LASCCHN patients ineligible for CDDP treatment, although attention to hematological toxicity should be paid.

Purpose: Although oxaliplatin 130 mg/m 2 every 3 weeks was approved for advanced gastric cancer in Japan, data regarding S-1 plus oxaliplatin 130 mg/m 2 (SOX130) are limited in Japanese patients with advanced gastric cancer. We investigated the feasibility and safety of SOX130 in Japanese patients with advanced gastric cancer., Methods: Patients with unresectable or recurrent gastric adenocarcinoma, no previous chemotherapy, and Eastern Cooperative Oncology Group Performance Status of 0-1 were treated with SOX130. The primary endpoint was the 3-cycle completion rate, defined as the proportion of patients who completed the first three cycles with ≥ 80% relative dose intensity of oxaliplatin., Results: Twenty-five patients were enrolled from April 2015 to 2016. The 3-cycle completion rate was 72.0% (90% confidence interval: 53.8-86.1), which was higher than the predetermined threshold rate of 50%. With the median number of cycles being 6 (range, 1-19+), grade 3 or 4 adverse events occurred in 10 patients (40%). Major grade 3 adverse events were anorexia (24%), thrombocytopenia (16%), and neutropenia (12%). No febrile neutropenia or treatment-related deaths occurred. Among 12 patients with measurable lesions, the overall response rate was 58.3%. Median progression-free and overall survival were 5.7 months (95% confidence interval 2.9-8.5) and 13.1 months (95% confidence interval 7.4-19.0), respectively., Conclusion: Results indicated that SOX130 was feasible in Japanese patients with advanced gastric cancer.

Background: The efficacy of primary prophylactic granulocyte colony-stimulating factor (G-CSF) in preventing febrile neutropenia (FN) in patients treated with docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy remains controversial. We compared the incidence of FN in patients treated with and without primary prophylactic G-CSF., Methods: We performed a retrospective analysis of 142 patients with locally advanced head and neck or esophageal cancer treated with TPF between January 2009 and March 2017. Among them, 116 patients started TPF without primary prophylactic G-CSF (control group) while 26 patients were given primary prophylactic G-CSF from day 7 of the first cycle of TPF (prophylactic group)., Results: The incidence of grade 4 neutropenia during the first cycle of TPF was significantly higher in the control group than in the prophylactic group [58.6% (n = 68) vs. 30.8% (n = 8), p = 0.02]. However, the incidence of FN in the first cycle was not significantly different between the two groups [32 patients (27.5%) in the control group and 8 patients (30.8%) in the prophylactic group (p = 0.62)]. In addition, the mean relative dose intensity throughout all cycles of TPF, as well as the survival time and response after TPF, were also not significantly different between the two groups., Conclusions: Primary prophylactic G-CSF from day 7 of the first cycle of TPF did not reduce the incidence of FN. Our findings suggest that the timing of primary prophylactic G-CSF, as recommended by the American Society of Clinical Oncology guidelines, should be modified to reduce the incidence of FN in TPF.

The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT3) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT3 receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT3 receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.

Background: We previously reported the pharmacokinetic profile and preliminary tolerability of cabazitaxel in a phase I study in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Here we report the final safety profile and anti-tumor activity of cabazitaxel in a larger population, including all patients enrolled in the expansion cohort of the study., Methods: Japanese patients with mCRPC previously treated with docetaxel received cabazitaxel intravenously every 3 weeks plus daily prednisolone. In patients treated with the maximum tolerated dose of 25 mg/m(2) we evaluated adverse events including treatment-related neutropenia, prostate-specific antigen (PSA) response and objective response., Results: In total, 44 patients were treated with the maximum tolerated dose. The most frequent adverse events (any grade) were neutropenia (100 %), febrile neutropenia (54.5 %), fatigue (54.5 %), nausea (52.3 %) and diarrhea (50.0 %). There were no deaths due to treatment-related adverse events. Neutropenia with prior docetaxel did not appear to influence the probability of febrile neutropenia with cabazitaxel. Most patients received therapeutic granulocyte colony-stimulating factor (G-CSF; cycle 1: 86.4 %; cycle 2 or later: 81.8 %). In the efficacy population, two of 12 patients with measurable disease had partial response (objective response rate: 16.7 %), while 10 had stable disease. PSA response rate was 29.3 % (12/41 patients). Median time to PSA progression was 3.68 months (95 % confidence interval 1.35-4.63)., Conclusions: In this heavily pretreated Japanese population, the occurrence of neutropenia and febrile neutropenia was high, suggesting G-CSF prophylaxis may be required as part of toxicity management. However, the efficacy of cabazitaxel was consistent with global studies. ClinicalTrials.gov identifier: NCT01324583.

Background: We evaluated the efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) with a high risk of distant metastases compared with CRT alone., Methods: We retrospectively analyzed 29 HNSCC patients with clinical nodal stage N2c, N3, or N2b disease and supraclavicular lymph node metastases receiving CRT alone (CRT group; n = 16) or TPF induction chemotherapy followed by CRT (TPF group; n = 13) between April 2008 and May 2012., Results: The median follow-up periods were 14.5 (range 5.0-65.0) and 25.0 (range 14.0-32.0) months for CRT and TPF groups, respectively. A greater proportion of patient characteristics in the CRT group had advanced T and N stages. The overall response rate to induction TPF was 50.0%; grade 3-4 toxicities included neutropenia, febrile neutropenia, anorexia, and hyponatremia. Complete response rates after CRT completion were 55.5% in the TPF and 42.9% in the CRT group; median overall survival was not reached in the TPF group and was 14.0 months in the CRT group (p = 0.037). Multivariate analysis revealed that induction TPF and T stage were independent prognostic factors [hazard ratio (HR) = 0.196; 95% confidence interval (CI) 0.043-0.898; p = 0.036, HR = 9.966; 95% CI 2.270-43.75; p = 0.002, respectively)., Conclusion: TPF followed by CRT is tolerated and may be an option for the treatment of locally advanced stage N2c, N3, or N2b HNSCC.

Background: The influence of resection of the primary lesion on the prognosis of patients with incurable stage IV colorectal cancer is unclear., Methods: We retrospectively analyzed 158 asymptomatic patients with incurable stage IV colorectal cancer who received systemic chemotherapy in our center from 2002 to 2009, either without (chemotherapy group; n = 112) or after (resection group; n = 46) primary tumor resection. Primary tumor resection was performed if the fiberscope did not pass through the primary lesion. Survival was compared between the 2 groups, and the actual surgical intervention was assessed., Results: At a median follow-up period of 26 months (range 7-91 months), the median survival times were 19.9 months in the resection group and 19.0 months in the chemotherapy group (HR = 0.81, 95 % CI 0.53-1.19, p = 0.29). Among the tumor resection group, 8 (17 %) experienced postoperative complications, with all showing improvement after conservative treatment. In the chemotherapy group, 18 patients (21 %) required surgical interventions for symptoms associated with progression of the primary tumor., Conclusions: Resection of the primary tumor in asymptomatic patients with incurable stage IV colorectal cancer was safe, but had no effect on prognosis.

Background: High-risk factors for recurrence of head and neck squamous cell carcinoma after surgical resection include involvement of ≥ 2 regional lymph nodes, extracapsular spread, and microscopic involvement of resected mucosal margins. Adjuvant chemoradiotherapy is thought to improve postoperative locoregional control and survival. In this paper, we evaluate the efficacy of adjuvant therapy for high-risk oropharyngeal squamous cell carcinoma (OPSCC) (i.e., with ≥ 2 lymph nodes, positive extracapsular spread, or positive margins)., Methods: This is a retrospective analysis of 45 high-risk OPSCC patients who underwent surgery without adjuvant therapy (n = 19), with radiotherapy (n = 17), or with chemoradiotherapy (n = 9)., Results: The median follow-up period was 41.0 months. Radiotherapy patients showed a trend toward longer overall survival than patients without adjuvant therapy [hazard ratio (HR) = 0.32, p = 0.176]. However, overall survival for the chemoradiotherapy group seemed to be the same as that for the no adjuvant therapy group (HR = 0.79, p = 0.779). Multivariate analysis found that the relative risk of recurrence for patients without adjuvant therapy compared with any adjuvant therapy was 3.02 (p = 0.101). The relative recurrence risk in radiotherapy patients was 0.95 compared with that in chemoradiotherapy patients (p = 0.971). However, pathological T-stage was significantly associated with disease-free survival for high-risk OPSCC., Conclusions: Although the current study uses data from a small retrospective sample of patients, our results suggest that the addition of chemotherapy to radiotherapy may not be necessary as an adjuvant therapy for all high-risk OPSCC. A novel prognostic factor, such as pathological T-stage, should be considered for selecting those patients with high-risk OPSCC who would benefit from adjuvant therapy.

Background: The number of cases of metastatic colorectal cancer treated by chemotherapy without primary tumor resection has recently increased. However, evaluation of primary tumor response by computed tomography is difficult in such cases. In this study, the usefulness of evaluation of primary tumor response to chemotherapy by endoscopy was investigated., Methods: This retrospective analysis was performed at the Shizuoka Cancer Center and included 31 patients (88 evaluations) with metastatic colorectal cancer. Computed tomography and endoscopy were performed concomitantly between September 2002 and June 2006. Patients were treated by systemic chemotherapy without prophylactic primary tumor resection. Definitions of primary tumor response were as follows: (1) complete response, confirmed by colorectal biopsy; (2) progressive disease, enlargement of at least one of five tumor parameters; and (3) neither (1) nor (2). Computed tomography was performed to evaluate primary tumor response according to the Response Evaluation Criteria in Solid Tumors and to identify colorectal stenosis secondary to primary tumors., Results: The rate of concordance between endoscopy and computed tomography for evaluation of primary tumor response was 75%. Colorectal stenosis was detected 14 times by endoscopy (9 cases) and 3 times by computed tomography (3 cases). Of the 7 patients in whom surgery was required, 6 exhibited stenotic symptoms before endoscopic detection., Conclusions: With regard to primary tumor response evaluation, a high concordance rate was observed between endoscopy and computed tomography, although endoscopic evaluation appeared more sensitive in detecting colorectal stenosis requiring surgical treatment.

Background: An oxaliplatin-based regimen as the adjuvant treatment for stage III colon cancer demonstrated a survival advantage over fluorouracil (FU) and leucovorin (LV) in the MOSAIC and NSABP C-07 trials. For adjuvant treatment after the resection of metastases from colorectal cancer), active chemotherapy regimens such as FOLFOX are recommended. However, the safety data of FOLFOX are insufficient for its use after metastasectomy of colorectal cancer in Japanese patients. The aim of this study was to evaluate the safety of mFOLFOX6 for adjuvant treatment after the resection of metastases from colorectal cancer., Methods: Among 67 consecutive patients who received mFOLFOX6 as the adjuvant treatment after resection of metastases from colorectal cancer between September 2002 and March 2009 in our institution, 51 patients who had not received preoperative chemotherapy were reviewed. The mFOLFOX6 treatment comprised oxaliplatin 85 mg/m(2) and l-leucovorin 200 mg/m(2) given intravenously over a 2-h period on day 1, followed by a 5-FU bolus of 400 mg/m(2) and a 46-h infusion of 5-FU 2400 mg/m(2), every 2 weeks for up to 12 cycles., Results: National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CTC) grade 3-4 toxicities per patient were: peripheral neuropathy 8%, allergic reaction 4%, aspartate transaminase (AST) 4%, febrile neutropenia 4%, nausea 2%, anorexia 2%, fatigue 2%, alanine transaminase (ALT) 2%, bilirubin 2%, neutrophils 49%, leukocytes 6%, and hemoglobin 2%; 71% of the patients completed the scheduled 12 cycles., Conclusion: Adjuvant therapy with mFOLFOX6 after resection of metastases from colorectal cancer is feasible for Japanese patients.

Background: Although S-1 plus cisplatin (SP) therapy is recognized as the standard treatment for advanced gastric cancer (AGC) in Japan, its safety and efficacy in elderly patients have not been investigated sufficiently., Methods: We retrospectively reviewed the data of 58 patients with AGC selected from 82 consecutive patients who were ≥70 years old and were treated with SP or S-1 monotherapy as the first-line therapy. In SP, S-1 (40 mg/m(2), bid) was administered for 3 weeks and cisplatin (60 mg/m(2)) on day 8, every 5 weeks. In S-1 monotherapy, S-1 (40 mg/m(2), bid) was administered for 4 weeks, every 6 weeks., Results: SP and S-1 was administered in 21 and 37 patients, respectively. There were some differences in patient characteristics between the treatment groups, such as histological type (P = 0.16); the presence of liver metastasis (P = 0.07); and the presence of peritoneal metastasis (P = 0.02). The incidences of grade 3/4 hematological toxicities were 57% (12/21) in the SP and 35% (13/37) in the S-1 group (P = 0.17). Those of non-hematological toxicities were 14% (3/21) and 14% (5/37) for anorexia, 10% (2/21) and 14% (5/37) for fatigue, and 5% (1/21) and 5% (2/37) for nausea in the SP and S-1 groups, respectively. Median progression-free survival and median overall survival in the SP and S-1 groups were 5.0 and 5.2 months, and 14.4 and 10.9 months, respectively., Conclusion: SP and S-1 therapy were both feasible in elderly patients, though there is the risk of a high incidence of hematological toxicities.

Background: Leptomeningeal carcinomatosis (LMC) is a rare but devastating complication of gastric cancer., Methods: The subjects were 12 gastric cancer patients who were diagnosed as having LMC at the Shizuoka Cancer Center between October 2002 and March 2009. We conducted a retrospective survey of the medical records of the study subjects and collected data on the clinical features, treatment modalities employed/outcomes, and survival of the patients., Results: Of the 12 patients, 9 (75%) were male, and the median age was 63 years. Histopathologically, the majority of the patients (83%) had diffuse-type adenocarcinoma. At the time of diagnosis of the LMC, the other major sites of metastasis were the peritoneum (75%) and lymph nodes (50%). The median duration from the diagnosis of gastric cancer to the diagnosis of LMC was 15.6 months. While the treatment strategy changed with time, intrathecal chemotherapy (n = 10), followed by whole brain irradiation (n = 7) and subsequent ventriculo-peritoneal shunt (n = 3) was performed in 10 of the patients. Improvement of neurological functions was observed in 6 of the 10 patients. The median overall survival time from the diagnosis of LMC in all the 12 patients was 60 days. One patient survived for a considerably long period of 532 days., Conclusions: Multidisciplinary treatment, including ventriculo-peritoneal shunt for LMC secondary to gastric cancer, may benefit selected patients, but further accumulation of clinical cases is necessary.

Background: Although concurrent chemoradiotherapy (CRT) is a standard treatment for esophageal cancer invading adjacent structures (T4-EC), arterio-esophageal fistula (AEF) occurs occasionally as a critical adverse event of T4-EC with CRT. The frequency, clinical course, and risk factors of AEF related to CRT are not well known., Methods: We retrospectively analyzed 48 patients with T4-EC invasion of the aorta who were treated with 5-fluorouracil, cisplatin, and concurrent radiotherapy at our institution between September 2002 and April 2009. Treatment-related AEF was defined as AEF without obvious tumor progression. We evaluated the frequency, clinical courses, and risk factors of AEF., Results: The median survival time was 10.6 months with a median follow-up time of 33.3 months. The 2-year survival rate was 25%. Treatment-related AEF was observed in 7 patients (14.6%) and 4 of them died of massive bleeding due to aortic AEF. In the other 3 patients with non-aortic AEF, hemorrhage could be arrested by transcatheter arterial embolization (TAE). In the univariate analysis of risk factors for AEF, lower serum cholesterol level was a risk factor for AEF (OR 14.7; 95% CI 1.58-137; P = 0.008)., Conclusions: Although CRT has a curative potential even for patients with T4-EC invading the aorta, we should be aware of the relatively high incidence of treatment-related AEF. TAE may be successful in rescuing a non-aortic AEF patient. Low serum cholesterol level may be a risk factor for AEF, but further investigation is needed.

Background: Efficacy and safety of irinotecan and cisplatin administration every 2 weeks (biweekly regimen) or 4 weeks (4-weekly regimen) in patients with pretreated unresectable or recurrent gastric cancer was retrospectively evaluated., Methods: Study patients comprised two cohorts: cohort 1, consisting of 31 patients received chemotherapy on a 4-weekly regimen; and cohort 2, consisting of 32 patients received chemotherapy on a biweekly regimen. In cohort 1, patients received irinotecan (70 mg/m(2)) on days 1 and 15 and cisplatin (80 mg/m(2)) on day 1 every 4 weeks; in cohort 2, patients received irinotecan (60 mg/m(2)) on day 1 and cisplatin (30 mg/m(2)) on day 1 every 2 weeks., Results: Response rates were for cohorts 1 and 2 were 26% (7/27) and 28% (7/25) in patients with measurable lesions, median progression-free survivals were 3.5 and 4.3 months, and median survival times after irinotecan and cisplatin initiation were 9.5 and 10.1 months, respectively. The incidence of grades 3 and 4 hematological toxicities in cohorts 1 and 2 were 74% and 44% for leukopenia, 81% and 53% for neutropenia, and 45% and 28% for anemia, respectively. Incidences of grades 3 and 4 nonhematological toxicities were 23% and 12% for nausea, 23% and 9% for vomiting, 19% and 12% for anorexia, and 6% and 6% for febrile neutropenia, respectively., Conclusion: Irinotecan plus cisplatin chemotherapy administered on a biweekly regimen was comparable in efficacy to a 4-weekly regimen and might be more feasible than the 4-weekly regimen.

Background: Bevacizumab (BV) prolongs overall survival and progression-free survival when combined with standard chemotherapy for metastatic colorectal cancer (mCRC). However, because this drug was approved in Japan only in 2007, there has been little experience in Japan. This study was conducted to evaluate retrospectively the safety of BV in clinical practice., Methods: Sixty-five consecutive mCRC patients who received BV at our institution between June 2007 and March 2008 were selected. All patients were treated with chemotherapy in combination with BV. We surveyed the medical records of all patients for adverse events (AEs). We assessed the AEs using the Common Terminology Criteria for Adverse Events version 3.0., Results: The characteristics of the subjects were: male, 45 patients; median age, 57 years; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, 62 patients; number of prior chemotherapy regimens 0/1/ > 2, 15/28/22 patients. The incidence of BV therapy-related AEs of all grades was: hypertension, 47.7%; proteinuria, 33.8%; bleeding, 35.3%; gastrointestinal (GI) perforation, 3.1%; thrombosis, 7.7%; and wound-healing complications, 6.2%. The incidence of grade 3/4 AEs related to BV therapy was: hypertension, 13.8%; bleeding, 1.5%; GI perforation, 1.5%; and thrombosis, 4.6%. Four patients (6.2%) had to stop chemotherapy because of the development of BV therapy-related AEs. New events of hypertension, bleeding, and proteinuria emerged until 120 days and thereafter., Conclusion: The incidence of BV therapy-related AEs in this study was consistent with that observed in Western prospective clinical trials, with the exception of hypertension and proteinuria. A careful follow up is recommended for up to 120 days after the initiation of BV administration.

Background: In Japan, chemotherapeutic agents that have been approved for the treatment of esophageal cancer include cisplatin, nedaplatin, 5-fluorouracil, vindesine, and docetaxel. We retrospectively investigated the efficacy and toxicity of a combination of nedaplatin plus vindesine, or docetaxel alone, for patients with unresectable or recurrent squamous cell carcinoma of the esophagus refractory to prior chemotherapy with 5-fluorouracil plus platinum., Methods: Nedaplatin was administered at 90 mg/m(2) intravenously on day 1, and vindesine was administered at 3 mg/m(2) intravenously on days 1 and 8 every 28 days. Docetaxel 60 mg/m(2) or 70 mg/m(2) was administered intravenously every 21 days. We analyzed the response rate, overall survival time, progression-free survival time, and toxicity in 24 patients treated with nedaplatin plus vindesine and 28 patients treated with docetaxel., Results: In patients treated with nedaplatin plus vindesine, the response rate of the 13 patients with measurable lesions was 8% (1/13), the median progression-free survival time was 1.8 months, and the median survival time was 5.5 months. In patients treated with docetaxel, the response rate of the 17 patients with measurable lesions was 18% (3/17), the median progression-free survival time was 2.1 months, and the median survival time was 5.1 months. The most frequent toxicity was neutropenia (grade 4; 13% in the group with nedaplatin plus vindesine and 50% in the docetaxel group), and febrile neutropenia (grade 3; 4% and 18%, respectively)., Conclusion: The efficacy of the two regimens for unresectable or recurrent squamous cell carcinoma of the esophagus refractory to chemotherapy with 5-fluorouracil plus platinum was unsatisfactory. New, more effective therapies are needed.

A patient was diagnosed with a small cell carcinoma of the esophagus (T4N1M1b by the International Union Against Cancer [UICC] classification) in October 2002, and initially received two courses of concurrent chemotherapy with 5-fluorouracil (5-FU; 400 mg/m(2) by continuous infusion; days 1-5 and 8-12) and cisplatin (40 mg/m(2) by drip infusion; days 1 and 8) and radiation therapy (2 Gy/day, days 1-5, 8-12, and 15-19; total, 30 Gy per course) with the second course given after a 2-week interval. Two courses of chemotherapy with 5-FU (800 mg/m(2); days 1-5) and cisplatin (80 mg/m(2); day 1) given after this was completed. Although a complete response had been confirmed, recurrence with multiple liver and lymph node metastases was detected 3 months after the cessation of the second course of chemotherapy. Although the patient received second-line chemotherapy with irinotecan (150 mg/m(2); every 2 weeks) from June 2003, the disease progressed. Brain metastases developed during third-line chemotherapy with gemcitabine (1000 mg/m(2) weekly by drip infusion). The symptoms were attenuated after whole-brain radiation (30 Gy), and fourth-line chemotherapy using paclitaxel (80 mg/m(2); weekly) was initiated from November 2003. A computed tomography scan 1 month after the first course of paclitaxel showed remarkable regression of the liver metastases. The treatment strategy used for treating small cell carcinomas of the lung may be applicable for these carcinomas of the esophagus.