Oxaliplatin as First-Line Treatment in Inoperable Biliary Tract Carcinoma

Androulakis, Nikolaos; Aravantinos, G.; Syrigos, Kostas; Polyzos, Aris; Ziras, Nikolaos; Tselepatiotis, E.; Samonis, George; Kentepozidis, Nikolaos; Giassas, Stylianos; Vamvakas, L.; Georgoulias, Vassilis

doi:10.1159/000096249

Cited by 23 publications

(17 citation statements)

References 37 publications

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“…However, no standard chemotherapy regimen for advanced BTC has been established. Several phase II trials with new chemotherapeutic agents, such as gemcitabine (6)(7)(8)(9)(10), capecitabine (11), oxaliplatin (12), or S-1 (13,14) have demonstrated tumor response in ~15-35% of patients treated with single agents, and in 20-40% of patients treated with their combinations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Among them, gemcitabine has shown promising activity against advanced BTC, and has been commonly used for patients with unresectable or recurrent BTC in Japan.…”

Section: Introductionmentioning

confidence: 99%

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

Nakamura

Kohya²,

Kai³

et al. 2010

Int J Oncol

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Abstract. Gemcitabine is a commonly used chemotherapeutic agent for advanced biliary tract carcinoma (BTC), although its efficacy is insufficient. Therefore, it is essential to establish new diagnostic methods, which can predict responders before the treatment. The aim of this study is to identify the most reliable chemoresistance marker to gemcitabine in BTC among the 4 molecules (hENT1, dCK, RRM1 and RRM2) involved in gemcitabine metabolism. The expression of 4 molecules were investigated in 5 BTC cell lines, and correlated with gemcitabine sensitivity. RRM1 protein was also assessed by quantitative double-fluorescence immunohistochemistry (qDFIHC) in 10 patients with unresectable or recurrent BTC who received gemcitabine-based chemotherapy. RRM1 and RRM2 protein strongly correlated with the IC 50 value for gemcitabine in BTC cell lines (R=0.935, 0.771, respectively). In addition, patients with low RRM1 were significantly more sensitive to gemcitabine (p=0.033), and their survival was significantly better than patients with high RRM1 (p=0.001).In conclusion, RRM1 particularly in protein level is a reliable marker for gemcitabine resistance in BTC. Furthermore, qDFIHC is a useful method for the assessment of RRM1 protein, in order to design a tailor-made chemotherapeutic regimen for BTC patients.

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Section: Introductionmentioning

confidence: 99%

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

Nakamura

Kohya²,

Kai³

et al. 2010

Int J Oncol

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“…Several small trials of combined regimens for GBC, using 5-FU, cisplatin, mitomycin and/or leucovorin, have been reported to have mixed results. Other chemotherapeutic agents that are now in clinical trials include capecitabine, oxaliplatin [5] , gemcitabine [6][7][8] , erlotinib [9] , etc. In addition, more and more people have paid their close attention to Chinese medicines for the prevention and treatment of cancer.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of gemcitabine-oxaliplatin combined with huachansu in patients with advanced gallbladder carcinoma

Qin¹,

Zhao²,

Yun³

et al. 2008

WJG

108

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A I M :To e v a l u a t e t h e e f f i c a c y a n d s a f e t y o f gemcitabine-oxaliplatin (GEMOX) combined with huachansu (cinobufagin) injection treatment in patients with locally advanced or metastatic gallbladder carcinoma (GBC), and to assess the quality of life (QOL) of such patients. METHODS: Twenty-five patients with locally advanced or metastatic GBC were treated with intravenous gemcitabine (1000 mg/m 2 ) over 30 min on days 1 and 8, 2 h infusion of oxaliplatin (120 mg/m 2 ) on day 1, and 2-3 h infusion of huachansu (20 mL/m 2 ) on days -3-11, every 3-4 wk. Treatment was continued until occurrence of unacceptable toxicity or disease progression. QOL of patients was assessed by the EORTC QLQ-C30 at baseline, at the end of the first, third and sixth chemotherapy cycles, and 1 mo after the treatment. RESULTS: Among the 25 patients with a median age of 64 years (range 42-78 years), 23 were evaluable in the study. A total of 137 cycles of therapy were performed and the median cycle was 5 (range 1-8) per patient. Out of the 23 patients whose response could be evaluated, 8 partial responses (PR) were observed (34.8%), while 7 patients (30.4%) demonstrated a stable disease (SD). The disease control rate was 65.2%. Progression of cancer was observed in 8 (34.8%) patients. The median progression-free and overall survival time was 5.8 mo (95% CI: 4.5-7.1 mo) and 10.5 mo, respectively. The therapy was well tolerated, with moderate myelosuppression as the main toxicity. Anemia grade 2 was seen in 16.0%, neutropenia grade 3 in 8.0% and thrombocytopenia grade 3 in 24.0% of patients, respectively. Nonhematologic toxicity ranged from mild to moderate. No death occurred due to toxicity. The QOL of patients was improved after chemotherapy, and the scores of QOL were increased by 10 to 20 points. CONCLUSION: GEMOX combined with huachansu (cinobufagin) injection is well tolerated, effective, thus improving the QOL of patients with advanced GBC.

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“…We have introduced oxaliplatin in the treatment of colorectal cancer both in advanced disease [19] as well as in the adjuvant setting and we have applied oxaliplatin in combination with other agents for the treatment of other gastrointestinal tumors such as stomach, pancreatic and biliary cancer [20,21,22]. As a result, several hypersensitivity reactions have been documented among our patients.…”

Section: Introductionmentioning

confidence: 99%

Clinical Features of Hypersensitivity Reactions to Oxaliplatin: A 10-Year Experience

Polyzos

Tsavaris²,

Gogas³

et al. 2008

Oncology

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Background: Oxaliplatin has become one of the major cytotoxic agents for the treatment of gastrointestinal tumors. As a result, several cases of the so-called oxaliplatin-associated hypersensitivity reaction have been documented. Patients and Methods: We have retrospectively evaluated and characterized these reactions in our patient group by reviewing the files of 1,224 patients exposed to an oxaliplatin-containing regimen in order to provide useful clinical information for diagnosis and management. Results: Three hundred and eight (308) patients who have never been exposed to platinum compounds developed symptoms compatible with a reaction to oxaliplatin that was verified by manifestation of at least similar symptoms on rechallenging. The reactions occurred after the first 5 courses, with a median course number of 9 (range 1–24). These reactions could be distinguished as (1) mild reactions occurring in 195 (63%) patients manifesting with itching and small area erythema either during treatment or within the next hours, and (2) severe reactions occurring in 113 (37%) patients within minutes of drug infusion manifesting with diffuse erythroderma, facial swelling, chest tightness, bronchospasm and changes in blood pressure. Oxaliplatin withdrawal was not required in patients with a mild reaction. Forty-eight (42%) patients having a severe reaction with appropriate premedication and prolongation of the infusion duration could tolerate 2–4 subsequent courses. For the remaining 65 (58%) patients, oxaliplatin withdrawal was inevitable because of the very severe reactions occurring on rechallenging. In addition, 3 patients presented with thrombocytopenia and 3 others with hemolytic anemia, all reversible upon oxaliplatin discontinuation. Conclusions: Hypersensitivity reactions to oxaliplatin are underestimated. Although the reactions are not frequent during first courses, in extensively pretreated patients, they may become a serious problem. In the majority of patients, drug discontinuation might not be necessary. In patients manifesting a severe reaction, re-exposure to oxaliplatin should be considered only if the patient can tolerate the reaction and there has been clinical benefit from this therapy. Physicians and nursing staff should be aware of the risk and be well prepared.

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Oxaliplatin as First-Line Treatment in Inoperable Biliary Tract Carcinoma

Cited by 23 publications

References 37 publications

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

Ribonucleotide reductase subunit M1 assessed by quantitative double-fluorescence immunohistochemistry predicts the efficacy of gemcitabine in biliary tract carcinoma

Efficacy and safety of gemcitabine-oxaliplatin combined with huachansu in patients with advanced gallbladder carcinoma

Clinical Features of Hypersensitivity Reactions to Oxaliplatin: A 10-Year Experience

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