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ABSTRACT: Abstract Background. Two standard sets of criteria are used to evaluate the tumor response of hepatocellular carcinoma (HCC): RECIST (Response Evaluation Criteria in Solid Tumors) and modified RECIST (mRECIST). The purpose was to compare two tumor response evaluation criteria, RECIST version 1.1 and mRECIST, for HCC treated using transcatheter arterial chemoembolization (TACE). Methods. The radiological findings of patients who underwent TACE for HCCs in a multicenter clinical trial were examined. Sixty-five lesions in 21 patients treated with TACE without mixing iodized-oil were evaluated. The tumor size was evaluated by measuring the entire lesion, including the necrotic part, using RECIST version 1.1, whereas only the contrast-enhanced part observed during the arterial phase was measured using mRECIST. Five radiologists independently measured each lesion twice. To evaluate the inter-criteria reproducibility, the complete response (CR) rate, the response rate, the kappa statistics, and the proportion of agreement (PA) for response categories were calculated. The same analyses were conducted for inter- and intra-observer reproducibility. Results. In the inter-criteria reproducibility study, the CR rate and the response rate obtained using mRECIST (56.9% and 79.7%) were higher than those obtained using RECIST version 1.1 (9.2% and 43.1%). In the inter- and intra-observer reproducibility study, mRECIST exhibited an 'almost perfect agreement', while RECIST version 1.1 exhibited a 'substantial agreement'. Conclusions. Considerable differences in the CR rate and the response rate were observed. From the viewpoint of the high inter- and intra-observer reproducibility, mRECIST may be more suitable for tumor response criteria in clinical trials of TACE for HCC.
Upsala journal of medical sciences 11/2012; · 0.73 Impact Factor
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Yasuaki Arai,
Atsushi Ohtsu, Yozo Sato,
Takeshi Aramaki,
Ken Kato,
Madoka Hamada,
Kei Muro,
Yasuhide Yamada,
Yoshitaka Inaba,
Yasuhiro Shimada,
Narikazu Boku,
Yoshito Takeuchi,
Sojiro Morita,
Mitsuo Satake
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ABSTRACT: Treatment of patients who have metastatic colorectal cancer (CRC) by using a combination of hepatic arterial infusion chemotherapy (HAIC) and systemic chemotherapy has resulted in promising clinical outcomes. Additionally, image-guided HAIC is reported to be less invasive and distribute drugs more accurately than surgical HAIC. The purpose of this study was to assess the combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan in a multicenter phase I/II study.
Twenty-five patients with unresectable liver metastases from CRC were fitted with hepatic arterial catheter and port systems by using image-guided methods. Intraarterial fluorouracil (1,000 mg/m(2)) was administered on days 1, 8, and 15 of each treatment cycle. The dose of systemic irinotecan on days 1 and 15 was escalated from 75 mg/m(2).
No dose-limiting toxicity was encountered during phase I, and the recommended dose of irinotecan was set at 150 mg/m(2). Grade 3 or higher adverse events included hyperglycemia (15%), elevated γ-glutamyl transpeptidase levels (15%), and neutropenia (9%). The response rate and median survival time were 72% and 49.8 months (95% CI, 27.5-78.1 mo), respectively.
The combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan yielded favorable safety, response rate, and survival results. This combination should be evaluated in a large study.
Journal of vascular and interventional radiology: JVIR 08/2012; 23(10):1261-7. · 1.81 Impact Factor
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ABSTRACT: A 37-year-old male presented with hepatic metastases from uveal melanoma after the enucleation of an affected eye. Hepatic metastases were thought to be the critical factors determining prognosis, so transcatheter arterial chemoembolization (TACE) was performed for local control of the hepatic metastases. The first TACE with cisplatin (CDDP) and gelatin sponge (GS) did not have much success because fine feeding arteries to the main hepatic tumor on the caudate lobe branched out from the hepatic artery, and GS particles were not distributed in the tumor vessels. We used degradable starch microspheres (DSM) as finer obstructing material for the next treatment, and hepatic metastases were treated effectively with repeated CDDP/DSM-TACE.
Gan to kagaku ryoho. Cancer & chemotherapy 06/2012; 39(6):959-61.
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ABSTRACT: BACKGROUND: There are few data on the efficacy of combination chemotherapy with a fluoropyrimidine plus cisplatin for patients with advanced or recurrent gastric cancer (AGC) complicated by peritoneal metastasis, especially massive ascites. METHODS: We retrospectively evaluated the efficacy and safety of a fluoropyrimidine (S-1 or capecitabine) plus cisplatin as first-line chemotherapy in 120 patients with AGC and peritoneal metastasis. RESULTS: Ascites was detected in 50 patients, with 11 patients having massive ascites. Median progression-free survival (PFS) and overall survival (OS) of all patients was 6.1 and 15.9 months, respectively. The PFS and OS were shorter in patients with massive ascites (n = 11; 3.7 and 9.5 months) compared with patients with small or moderate ascites (n = 39; 5.8 and 13.5 months) or patients without ascites (n = 70; 6.9 and 18.1 months). The objective response in terms of ascites was similar whether ascites was massive (4 of 11 patients; 36.4%) or small or moderate (16 of 39 patients; 41%). The frequencies of grade 3 or higher toxicity or treatment discontinuation due to toxicity are relatively similar across ascites groups. CONCLUSIONS: Fluoropyrimidine plus cisplatin appears to be tolerated in selected patients with peritoneal metastasis.
Gastric Cancer 02/2012; · 2.42 Impact Factor
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Kohei Shitara,
Keitaro Matsuo,
Chihiro Kondo,
Daisuke Takahari,
Takashi Ura,
Yoshitaka Inaba,
Hidekazu Yamaura, Yozo Sato,
Mina Kato,
Yukihide Kanemitsu,
Koji Komori,
Seiji Ishiguro,
Tsuyoshi Sano,
Yasuhiro Shimizu,
Kei Muro
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ABSTRACT: The ability of molecular targeting agents to improve overall survival (OS) in metastatic colorectal cancer (MCRC) patients who underwent oxaliplatin-based chemotherapy remains controversial.
We retrospectively analyzed 331 patients with MCRC who underwent first-line oxaliplatin-based chemotherapy. Treatment outcomes were compared between patients who started chemotherapy from April 2005 to March 2007 (cohort A; n = 157) and those who started it from April 2007 to March 2009 (cohort B; n = 174). To evaluate the impact of exposure to agents, we applied time-varying covariate analysis to avoid possible lead-time bias.
Median OS of cohorts A and B was 21.3 and 28.6 months, respectively (HR 0.66, 95% CI 0.50-0.87, p = 0.003). Exposure to bevacizumab (25 vs. 76%), anti-epidermal growth factor receptor (EGFR) (18 vs. 33%) or curative surgery after chemotherapy (4 vs. 10%) was significantly higher in cohort B. According to a multivariate Cox model with exposure to each agent or treatment as a time-varying covariate, hazard ratios of death were 0.71 (95% CI, 0.51-0.96; p = 0.03) for bevacizumab, 0.62 (95% CI, 0.40-0.89; p = 0.01) for anti-EGFR and 0.22 (95% CI, 0.06-0.57; p = 0.004) for surgery.
Increased exposure to molecular targeting agents or surgery after chemotherapy appears to contribute to an improvement in OS in recent patients with MCRC who have undergone oxaliplatin-based chemotherapy.
Oncology 11/2011; 81(3-4):167-74. · 2.27 Impact Factor
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Kohei Shitara,
Keitaro Matsuo,
Tomoya Yokota,
Daisuke Takahari,
Takashi Shibata,
Takashi Ura,
Yoshitaka Inaba,
Hidekazu Yamaura, Yozo Sato,
Mina Najima,
Kei Muro
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ABSTRACT: No reports about factors that predict prognosis after second-line chemotherapy for metastatic colorectal cancer have been published.
We retrospectively analyzed 124 patients with metastatic colorectal cancer who received irinotecan-based second-line chemotherapy after first-line folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX) with or without bevacizumab.
A multivariate Cox model revealed 5 prognostic factors for worse survival: ECOG performance status 2, pathologically poorly differentiated adenocarcinoma, peritoneal metastasis, progression-free survival of first-line FOLFOX < 6 months, and lactate dehydrogenase ≥ 400 IU/L. When patients were categorized into 3 risk groups-patients without any prognostic factors (low-risk, n = 55), patients with one prognostic factor (intermediate-risk, n = 32), and patients with 2 or more prognostic factors (high-risk, n = 37)-overall survival from initiation of second-line chemotherapy was 23.5, 14.6, and 5.5 months, respectively. The proportion of patients who were eligible to receive further chemotherapy after disease progression was significantly lower in the high-risk group (41%) than in the intermediate- (67%) and low-risk (95%) groups.
Several prognostic factors for survival after second-line therapy and probability of receiving third-line chemotherapy were identified. This risk classification system might be useful for determining which patients should receive cetuximab in the second-line setting rather than the third-line setting.
Gastrointestinal cancer research: GCR 09/2011; 4(5-6):168-72.
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Kohei Shitara,
Tomoya Yokota,
Daisuke Takahari,
Takashi Shibata,
Takashi Ura,
Setsuo Utsunomiya,
Yoshitaka Inaba,
Hidekazu Yamaura, Yozo Sato,
Mina Najima,
Hiroki Kawai,
Masahiro Tajika,
Akira Sawaki,
Yasushi Yatabe,
Kei Muro
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ABSTRACT: The aim of this study was to prospectively evaluate the efficacy of combination irinotecan and cetuximab chemotherapy in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. KRAS status was evaluated using the Cycleave PCR method; only patients without KRAS mutations were included. Cetuximab was administered initially at 400 mg/m² followed by weekly 250 mg/m² infusions. Irinotecan was administered biweekly. From October 2008 to April 2009, a total of 30 patients were enrolled. The objective response rate was 30.0% (95% confidence interval [CI], 14.7-49.4%) and the disease control rate (complete response, partial response, or stable disease) was 80.0% (95% CI, 61.4-92.3%). Among the 15 patients with stable disease, 11 patients experienced >10% tumor shrinkage. Median progression-free survival was 5.8 months (95% CI, 4.1-7.6). Median overall survival was not reached at a median follow-up of 10.1 months. Grade 2 skin toxicity was observed in 23 patients, while no grade 3 skin toxicity was observed. Combined irinotecan and cetuximab is effective for pretreated metastatic wild-type KRAS colorectal cancer.
Investigational New Drugs 08/2011; 29(4):688-93. · 3.36 Impact Factor
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Kohei Shitara,
Takashi Ura,
Keitaro Matsuo,
Daisuke Takahari,
Tomoya Yokota,
Satoshi Yuki,
Motoki Yoshida,
Setsuo Utsunomiya, Yozo Sato,
Hidekazu Yamaura,
Mina Kato,
Yoshitaka Inaba,
Masahiro Tajika,
Hiroki Kawai,
Kentaro Yamazaki,
Yoshito Komatsu,
Kei Muro
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ABSTRACT: The aim of this study was to evaluate the association of sensitivity to previous irinotecan-based chemotherapy with efficacy of cetuximab plus irinotecan therapy in metastatic colorectal cancer (MCRC) patients with wild-type KRAS. We analysed a pooled data set consisting of data from 87 MCRC patients from two previous phase II studies (n=60) and a group given off-protocol treatment (n=27) following irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. Overall objective response rate to cetuximab plus irinotecan was 28.7%, median progression-free survival (PFS) was 5.3 months, and median overall survival was 12.2 months. Objective response rate did not significantly differ between patients with a favourable response to previous irinotecan (n=23), stable disease (n=38), or progressive disease (n=26), with observed rates of 29.2%, 31.6%, and 23.1%, respectively. Additionally, the non-parametric Spearman rank correlation coefficients (ρ) between the PFS of previous irinotecan-based chemotherapy and that of cetuximab plus irinotecan were quite low (ρ=0.067 and 0.057 in patients with previous irinotecan as first- and second-line therapies, respectively). Although exploratory nature and small sample size may be limitations of this study, these findings indicate that the efficacy of irinotecan plus cetuximab in MCRC patients with wild-type KRAS did not differ by previous sensitivity to irinotecan.
European journal of cancer (Oxford, England: 1990) 06/2011; 47(18):2673-80. · 4.12 Impact Factor
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ABSTRACT: The purpose of this study was to investigate retrospectively the clinical procedural performance of CT-guided needle biopsy for retroperitoneal lesions.
CT-guided needle biopsy was performed in 74 consecutive patients (M:F = 44:30; mean age, 59.7 years) with retroperitoneal lesions between April 1998 and June 2009. The target lesion ranged from 1.5 to 12.5 cm in size. The biopsy access path ranged from 3.5 to 11.5 cm in depth. A biopsy specimen was obtained using an 18-gauge core needle under a CT or CT-fluoroscopy guidance and with the patient under local anesthesia. The histopathological diagnoses from the biopsies were obtained. The diagnostic confirmation of the subtype of lymphoma was evaluated.
Satisfactory biopsy samples were obtained in 73 (99%) of 74 patients and a pathological diagnosis was made in 70 (95%) of 74 patients. Sixty three lesions were malignant (45 lymphomas, nine primary tumors, nine lymph node metastases) and seven were benign. The subtype of lymphoma was specified in 43 (96%) of 45 patients who were diagnosed with lymphoma. Analysis of the value of CT-guided biopsy in this series indicated 63 true positives, zero false positive, six true negatives and five false negatives. This test had a sensitivity of 93%, a specificity of 100% and an accuracy of 93%. No major complications were seen and minor complications were noted in seven patients (five with local hematomas, two with transient pain at the puncture site).
CT-guided needle biopsy for retroperitoneal lesions is highly practical and useful, and particularly for determining the subtypes in patients with lymphoma.
Korean journal of radiology: official journal of the Korean Radiological Society 05/2011; 12(3):351-7. · 1.32 Impact Factor
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Clinical Colorectal Cancer 03/2011; 10(1):7. · 1.68 Impact Factor
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Ayako Mizota,
Kohei Shitara,
Chihiro Kondo,
Motoo Nomura,
Tomoya Yokota,
Daisuke Takahari,
Takashi Ura,
Yoshitaka Inaba,
Hidekazu Yamaura, Yozo Sato,
Mina Kato,
Kei Muro
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ABSTRACT: The efficacy and safety of cetuximab for irinotecan-intolerant patients has not yet been evaluated in detail.
We retrospectively analyzed the efficacy and safety of cetuximab monotherapy for patients with metastatic colorectal cancer (MCRC) that was intolerant to irinotecan.
Among 105 patients who received cetuximab-containing chemotherapy until March 2010, 22 patients were treated with cetuximab monotherapy due to irinotecan intolerance. Cetuximab was given at the approved dosage to all patients. The performance status was 2 or 3 in 17 patients (77%). All but 1 patient had wild-type KRAS tumors. The causes of irinotecan intolerance were icterus (n = 9; 41%; median serum total bilirubin, 6.3 mg/dl), symptomatic peritoneal metastasis or obstruction (n = 8; 36%), and thrombocytopenia (n = 1; 5%). Four patients (18%) refused irinotecan due to previous irinotecan-associated toxicity. Two patients achieved a partial response with an apparent drop of serum bilirubin, for a response rate of 9.1%. The median progression-free survival and overall survival were 1.6 and 3.5 months, respectively. No grade 3 or 4 adverse events or treatment-related deaths were experienced.
Cetuximab monotherapy for irinotecan-intolerant MCRC is feasible. However, the overall efficacy was modest in the present cohort, despite the fact that most of the patients had wild-type KRAS tumors; further effective therapies should be evaluated to improve the prognosis of this patient population.
International Journal of Clinical Oncology 03/2011; 16(4):416-20. · 1.41 Impact Factor
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ABSTRACT: A phase II study of stent therapy for unresectable malignant colorectal obstruction was conducted to ascertain the clinical efficacy, safety, and procedural feasibility.
Inclusion criteria comprised unresectable obstruction of the rectum or sigmoid colon; no other apparent stenosis; performance status by Eastern Cooperative Oncology Group ≤3; and maintained major organ function. The treatment protocol was to place an uncovered metal stent through the anus in an obstructive portion under x-ray fluoroscopic guidance. The patients were followed for 4 weeks after therapy, and the degree of improvement in subjective symptoms lasting ≥2 weeks was assessed as effective when the patient was decompressed with stent, or ineffective when not decompressed. Rate of clinical efficacy was defined as the proportion of effective cases.
The participants of the study comprised 33 patients (13 men and 20 women; mean age, 60 y). Rate of procedure completion was 97.0% (32/33). Treatment was effective in 27 patients, ineffective in 4, and unassessable in 1, yielding a clinical efficacy rate of 81.8% (27/33). Death owing to underlying disease (n=3), stent removal owing to anal pain (n=1), and occlusion at another location (n=1) were noted. No recurrences were seen among clinically effective cases. Adverse reactions included grades 2 to 3 diarrhea (n=12), pain (n=5), bleeding (n=1), and dysuria (n=1), but no grade 4 adverse reactions or treatment-related deaths were identified.
Stent therapy for unresectable malignant colorectal obstruction is effective, safe, and feasible.
American journal of clinical oncology 02/2011; 35(1):73-6. · 2.21 Impact Factor
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ABSTRACT: Equivalent cross-relaxation rate (ECR) imaging (ECRI) is a measurement technique that can be used to quantitatively evaluate changes in structural organization and cellular density by MRI. The aim of this study was to evaluate the correlation between the ECR value and cellular density in the rabbit VX2 tumor model.
Five rabbits implanted with 10 VX2 tumors in the femur muscles were included in this study. We adopted the off-resonance technique with a single saturation transfer pulse frequency of 7 ppm downfield from water resonance. The ECR value was defined as the percentage of signal loss between the unsaturated and saturated images. ECR images were constructed based on the percentage of the ECR value. Pathological specimens were divided into 34 areas and classified into two groups: the viable group and the necrotic group. ECR values were measured and compared between groups. The correlation between the ECR value and cellular density was then determined.
The mean ECR value was significantly higher in the viable group than in the necrotic group (61.2% vs. 35.8%). The area under the curve that calculated by receiver operating characteristic curve was 0.991 at 7 ppm. The regression graph showed a linear relationship between the ECR value and cellular density; the correlation coefficient (r) was 0.858.
There is a strong association between the ECR value and cellular density in VX2 tumors and so ECRI could be a potentially useful technique for accurately depicting viable and necrotic areas.
Cancer informatics 01/2011; 10:227-32.
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ABSTRACT: This retrospective study evaluated the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil (5-FU) for patients with liver metastases from colorectal cancer refractory to standard systemic chemotherapy.
Fifty-five patients who had shown disease progression during the prior standard systemic chemotherapy with oxaliplatin, irinotecan, and 5-FU were enrolled. The treatment was weekly HAIC with 5-FU 1000 mg/m2/5 hours through an indwelling catheter-port system.
No major adverse reaction was observed other than grade 3 leukocytopenia (3.6%) and hyperbilirubinemia (1.8%). The overall response rate and disease control rate were 18.2% and 70.9%, respectively. The median progression-free survival and median overall survival (OS) were 2.8 months, and 6.7 months, respectively. The initial sites of disease progression were liver in 14, other than liver in 27, and both in 6. Multivariate analysis identified Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1 and number of extrahepatic metastatic sites (NMS) ≤ 1 as favorable prognostic factors for OS (hazard ratio [HR], 8.277; 95% CI, 3.60-19.0; P = .000 for ECOG PS; and HR, 2.456; 95% CI, 1.30-4.61; P = .005 for NMS).
HAIC with 5-FU may be a safe and effective treatment for patients with colorectal liver metastases refractory to standard systemic chemotherapy.
Clinical Colorectal Cancer 12/2010; 9(5):305-10. · 1.68 Impact Factor
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Kohei Shitara,
Satoshi Yuki,
Motoki Yoshida,
Daisuke Takahari,
Setsuo Utsunomiya,
Tomoya Yokota, Yozo Sato,
Yoshitaka Inaba,
Masahiro Tajika,
Hiroki Kawai,
Hidekazu Yamaura,
Mina Kato,
Kentaro Yamazaki,
Yoshito Komatsu,
Kei Muro
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ABSTRACT: The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with every second week cetuximab and irinotecan in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with wild-type KRAS metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. Cetuximab was administered at 500 mg/m(2) biweekly with irinotecan. The primary endpoint was response rate. The pharmacokinetics of cetuximab was also evaluated in 5 patients. From May 2009 to February 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 patients who were treated with biweekly cetuximab plus irinotecan, partial response was observed in 9 patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7%-49.4%) and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95% CI, 57.7%-90.0%). The median progression-free survival was 5.3 months and median overall survival was 10.8 months. Grade 3 skin toxicity was observed in 3 patients (10.0%) and one treatment related death due to pneumonia was observed. Combination chemotherapy with biweekly cetuximab and irinotecan was effective for pretreated metastatic colorectal cancer with wild-type KRAS.
Investigational New Drugs 12/2010; 30(2):787-93. · 3.36 Impact Factor
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Shunsuke Sugawara,
Miyuki Sone,
Yasuaki Arai,
Noriaki Sakamoto,
Takeshi Aramaki, Yozo Sato,
Yoshitaka Inaba,
Yoshito Takeuchi,
Teruko Ueno,
Kiyoshi Matsueda,
Michihisa Moriguchi,
Takahiro Tsushima
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ABSTRACT: Peritoneal venous shunts (PVSs) are widely used for palliating symptoms of refractory malignant ascites and are recognized as one of the practical methods. However, reliable clinical data are insufficient because most previous reports have been small studies from single centers. We conducted a retrospective, multicenter study to evaluate the safety and efficacy of radiologically placed PVSs in patients with malignant refractory ascites.
A total of 133 patients with malignant ascites refractory to medical therapies were evaluated for patient characteristics, technical success, efficacy, survival times, adverse events, and changes in laboratory data.
PVSs were successfully placed in all patients and were effective (i.e., improvement of ascites symptoms lasting 7 days or more) in 110 (82.7%). The median duration of symptom palliation was 26 days and median survival time was 41 days. The most frequent adverse event was PVS dysfunction, which occurred in 60 (45.1%) patients, among whom function was recovered with an additional minimally invasive procedure in 9. Abnormalities in coagulation (subclinical disseminated intravascular coagulation) occurred in 37 (27.8%) patients, although only 7 (5.3%) developed clinical disseminated intravascular coagulation. Other major adverse events were gastrointestinal bleeding (9.8%), sepsis (3.8%), and acute heart failure (3.0%). PVS was least effective in patients with elevated serum creatinine, bloody ascites, or gynecologic tumor.
Radiological PVS is a technically feasible and effective method for palliating the symptoms from refractory malignant ascites, but preoperative evaluation and monitoring the postprocedural complications are mandatory to preclude severe adverse events after PVS.
CardioVascular and Interventional Radiology 12/2010; 34(5):980-8. · 2.09 Impact Factor
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Yoshitaka Inaba,
Yasuaki Arai,
Hidekazu Yamaura, Yozo Sato,
Mina Najima,
Takeshi Aramaki,
Miyuki Sone,
Takashi Kumada,
Noboru Tanigawa,
Hiroshi Anai,
Tetsuya Yoshioka,
Masafumi Ikeda
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ABSTRACT: No established therapy exists for unresectable intrahepatic cholangiocarcinoma (ICC). We conducted a phase I/II study to ascertain the recommended dose (RD) of hepatic arterial infusion using gemcitabine (GEM) for ICC and to assess the efficacy and safety.
For patients with unresectable ICC, GEM was administered through the hepatic artery via the port system as a 30-minute infusion on days 1, 8, and 15 every 4 weeks for 5 cycles. In phase I, dosage for levels 1, 2, and 3 was set at 600, 800, and 1000 mg/m, respectively, and was increased in 3 to 6 patients at a time. Maximum tolerated dose was defined as a dosage resulting in dose-limiting toxicity in 2 of 3 patients or 3 of 6 patients, and RD was estimated during the first cycle. In the phase II, more RD patients were added to assess tumor response and toxicity.
During the phase I, 16 patients were enrolled. Maximum tolerated dose was not reached. Assuming RD at 1000 mg/m, the phase II enrolled a total of 13 patients. The following Grade 3 toxicities were observed: neutropenia 20%, increased gamma-glutamyl transpeptidase 8%, increased aspartate aminotransferase 4%, increased alanine aminotransferase 4%, increased bilirubin 4%, nausea 4%, and fatigue 4%. The tumor response rate was 7.7% (complete response 0, partial response 1, stable disease 8, and progressive disease 4).
Whereas the toxicity of hepatic arterial infusion with 1000 mg/m GEM for ICC was tolerable, expected efficacy could not be obtained, thus suggesting only minimal activity.
American journal of clinical oncology 02/2010; 34(1):58-62. · 2.21 Impact Factor
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ABSTRACT: Cetuximab-based chemotherapy showed a statistically significantly higher response rate compared with chemotherapy such as FOLFOX. Therefore, FOLFOX plus cetuximab is suspected to be the best regimen to alleviate tumor-related symptoms with a high response rate.
Here we present the results of 8 consecutive patients with metastatic colorectal cancer with poor performance status and/or severe complications who were treated with first-line FOLFOX with cetuximab. Six of 8 patients achieved an apparent clinical benefit, including radiological response and symptoms improvement. Two patients with BRAF mutation could achieve neither clinical benefit nor radiological response.
Although an optimal line of therapy with cetuximab is unclear yet with bevacizumab in mind, we propose that patients who need a tumor response to alleviate their symptoms due to advanced disease might be candidates for first-line cetuximab-based therapy as shown in our cases. Additionally, patients with BRAF mutant tumors might be important candidates for novel targeted therapy in the future to improve their poor prognosis.
Case Reports in Oncology 01/2010; 3(2):282-6.
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ABSTRACT: This paper is an overview of the new response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1), with a focus on updated contents.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2009; 36(13):2495-501.
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Kohei Shitara,
Daisuke Takahari,
Tomoya Yokota,
Takashi Shibata,
Takashi Ura,
Kei Muro,
Yoshitaka Inaba,
Hidekazu Yamaura, Yozo Sato,
Mina Najima,
Setsuo Utsunomiya
Japanese Journal of Clinical Oncology 11/2009; 40(3):275-7. · 1.78 Impact Factor
