Properties of the Measures to Assess Oxaliplatin-induced Peripheral Neuropathy: A Literature Review

PURPOSE: The purpose of this study is to provide a comprehensive overview of the various measures available for assessment of oxaliplatin-induced peripheral neuropathy (OXLIPN) and to evaluate the measurement properties of each assessment tool. METHODS: A systematic review was conducted to identify existing measures for OXLIPN found in the databases of PubMed, Cochrane Library, Embase, RISS and KoreaMed. The quality of the 24 identified tools was evaluated based on their properties of measurement including content validity, internal consistency, criterion validity, construct validity, reproducibility, responsiveness, floor-ceiling effects and interpretability. RESULTS: Ten (41.7%) of the 24 tools were identified as specific measures for assessing OXLIPN and the most popular type of measures were clinical grading systems by clinicians (58.3%) and only 29.2% of measures were identified as patient reported outcomes. The most frequently used tool was National Cancer Institute-Common Toxicity Criteria (NCI-CTC), but the validity of NCI-CTC has not been reported appropriately. Overall, the Neuropathic Pain Symptom Inventory (NPSI) received the best psychometric scores, and the Chemotherapy-induced Peripheral Neuropathy Assessment Tool (CIPNAT) and Functional Assessment of Cancer Therapy/Gynaecologic Oncology Group-neurotoxicity-12 (FACT/GOG-Ntx-12) followed NPSI. CONCLUSION: To select appropriate measure, evidences should be accumulated through the clinical use of tools. Therefore, practitioner and researchers are urged to report relevant statistics required for the validation of the currently used measures for assessment of OXLIPN.

Efficacy and Safety of FOLFIRI after Failure of FOLFOX-4 in Advanced Gastric Cancer / 대한소화기학회지

BACKGROUND/AIMS: The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer. METHODS: Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0. RESULTS: Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP. CONCLUSIONS: FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.

Sinusoidal obstruction syndrome after oxaliplatin-based chemotherapy

No abstract available.

Trombosis venosa portal e hiperplasia nodular regenerativa hepática; posible efecto adverso asociado a bevacizumab y oxaliplatino / Portal vein thrombosis and nodular regenerative hyperplasia associated with the use of bevacizumab and oxaliplatin. Report of one case

Nodular regenerative hyperplasia (NRH) consists in diffuse transformation of the hepatic parenchyma into small regenerative nodules without fibrosis, secondary to vascular occlusion and flow alterations. This gives a nodular appearance to theliver, as there is atrophy and compensatory hypertrophy of hepatocytes. We reporta 69-year-old male who suffered of colon cancer and was treated with Oxaliplatin (OX) and Bevacizumab (B). During treatment with B the patient presented a partial thrombosis of the portal vein, that one year later became permeable. Esophageal varices were found in an upper digestive endoscopy. Hepatic tests were normal. Aliver biopsy was performed and informed nodular regenerative hyperplasia. Thus, the different factors that could explain this pathology are analyzed. B, a monoclonal antibody against vascular endothelial growth factor, reduces the anti-apoptotic, anti-inflammatory and survival effects produced by this factor, affecting the vascular protection of the endothelial cell. On the other hand, OX activates metalloproteinasesand depletes sinusoidal glutathione producing sinusoidal lesions. Thus, (OX) would be associated with sinusoidal obstruction and NRH sporadically. It is important to discuss the possible etiologic factors that can cause NRH reviewing the hepatotoxic effects caused by both drugs.

Vitamin E for prevention of oxaliplatin-induced peripheral neuropathy: a pilot randomized clinical trial / Vitamina E na prevenção de neuropatia periférica induzida pela oxaliplatina: estudo clínico piloto randomizado

Oxaliplatin is one of the chemotherapy regimens most used for treating colorectal cancer. One of the main limitations to its use is induction of peripheral neuropathy. Previous studies have shown that vitamin E can reduce the incidence of peripheral neuropathy by 50%. This study aimed to assess the effectiveness of vitamin E for prevention of oxaliplatin-induced peripheral neuropathy.

Prospective, phase II, randomized pilot study developed at a university hospital in the Greater ABC region.

Patients were randomized five days before starting oxaliplatin treatment, to receive either vitamin E or placebo until the end of the chemotherapy regimen. The outcome was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3, and specific gradation scales for oxaliplatin-induced peripheral neuropathy. Patients with colorectal and gastric cancer who had been scheduled to receive oxaliplatin-based chemotherapy were included. Both groups received calcium and magnesium supplementation before and after oxaliplatin infusions.

Eighteen patients were randomized to the vitamin E group and 16 to the placebo group. Cumulative incidence of 83% with peripheral neuropathy grades 1/2 was observed in the vitamin E group, versus 68% in the placebo group (P = 0.45). A trend towards more diarrhea was observed among patients who received vitamin E (55.6% vs. 18.8%; P = 0.06). There were no other significant differences in toxicity between the groups.

No significant decrease in the incidence of acute oxaliplatin-induced peripheral neuropathy was demonstrated through vitamin E use.

A oxaliplatina é um dos quimioterápicos mais utilizados no tratamento do câncer colorretal, sendo a indução da neuropatia periférica (NP) uma das principais limitações para o seu uso. Trabalhos anteriores demonstraram que a vitamina E poderia reduzir a incidência dessa neuropatia em 50%. Este estudo teve como objetivo avaliar a efetividade da vitamina E na prevenção da NP induzida pela oxaliplatina.

Estudo piloto prospectivo e randomizado de fase II desenvolvido em hospital universitário do Grande ABC.

Os pacientes foram randomizados para receber vitamina E ou placebo por cinco dias antes do início do tratamento com oxaliplatina e até o término do regime quimioterápico. O desfecho foi avaliado através dos Critérios Comuns de Toxicidade do Câncer versão 3 (CTCAE) e escalas específicas de gradação da NP induzida por oxaliplatina. Foram incluídos pacientes com câncer colorretal e gástrico programado para receber quimioterapia baseada em oxaliplatina. Ambos os grupos receberam suplementação de cálcio e magnésio antes e depois das infusões de oxaliplatina.

Dezoito pacientes foram randomizados para grupo da vitamina E e 16 para o grupo placebo. Observou-se incidência cumulativa de 83% das classes I/II de neuropatia periférica no grupo da vitamina E, contra 68% no grupo placebo (P = 0,45). Observou-se maior tendência à diarreia em pacientes que receberam vitamina E (55,6% versus 18,8%, P = 0,06). Não houve outras diferenças significativas quanto às toxicidades entre os grupos. ...

Biweekly peglated liposomal doxorubicin/oxaliplatin for ovarian cancer resistant to taxane-platinum treatment: A Phase II study.

Aim: The aim of this Phase II study was to evaluate the activity and safety of biweekly pegylated liposomal doxorubicin (PLD) and oxaliplatin (L-OHP) in patients with platinum-taxane resistant ovarian cancer. Materials and Methods : Treatment consisted of PLD (20 mg/m 2 ) on Day 1; and L-OHP (50 mg/m 2 ) administered on Days 1 and 2, every two weeks. Response to therapy was assessed using the Response Evaluation Criteria in Solid Tumors RECIST ; toxicity was evaluated by the National Cancer Institute Common Toxicity Criteria. Results: Forty patients pretreated with platinum/taxane chemotherapy, with a median age of 61 years, were recruited for the study. Thirty-eight patients were available for response evaluation: three complete responses and nine partial responses were registered; resulting in an overall response rate of 31.5%. Twenty-eight patients gained clinical benefit (73.7%) from this chemotherapy regimen. Median time to progression (TTP) and overall survival (OS) were 5.5 and 10 months respectively. The hematological and non-hematological toxicity profile was favorable. No Grade 4 toxicity was observed. Major toxicities included Grade 3 neutropenia (13.2%), Grade 2 palmar-plantar erythrodysesthesia (7.9%), and Grade 1-2 neuropathy in 15.8% of patients. Conclusion: Biweekly PLD and L-OHP combination has high activity, with less than anticipated adverse toxicity, for treatment of platinum-resistant ovarian cancer. A comparison of the doublet PLD/L-OHP with single-agent treatment is warranted.

FOLFOX (oxaliplatin and 5fluorouracil/leucovorin) in patients with untreated metastatic gastric adenocarcinoma Phase II study.

Background: Oxaliplatin has shown promising activity in metastatic gastric cancer (MGC) and has synergism with 5 fluorouracil. This phase II study was performed to evaluate the efficacy and safety of FOLFOX4 regimen in MGC. Materials and Methods: Patients with MGC, aged 18-70 years, performance status ≤2, no prior chemotherapy, received FOLFOX4 regimen every 2 weeks as oxaliplatin 85 mg/m 2 IV infusion on day 1 and leucovorin 200 mg/m 2 IV infusion followed by fluorouracil 400 mg/m 2 IV bolus and 600 mg/m 2 22-hour continuous infusion on days 1 and 2. Treatment was administered until progression, unacceptable toxicity, patient's refusal or for a maximum of 12 cycles. Results: From August 2007 to June 2010, 34 patients were prospectively enrolled. The median age was 52 years (28-69). In total, 293 cycles were administered with a median of 8 cycles per patient (range 1-12 cycles) and 33 of 34 patients were assessable for treatment response. The overall response rate were 53% with one patient(3%) had complete response, 17 patients (50%) had partial responses and 6 patients (18%) had stable disease. The median survival of all patients was 12.1 months and the median time to progression was 9.4 months. The most common grade 3/4 toxic effects were neutropenia in four patients (12%), diarrhea in three patients (9%), vomiting in two patients (6%) and peripheral neuropathy occurred in three patients (9%). Conclusions: The FOLFOX4 combination chemotherapy showed a very promising antitumor activity and was generally well-tolerated as a first-line treatment of patients with MGC.

A Case of Portal Hypertension after the Treatment of Oxaliplatin Based Adjuvant-Chemotherapy for Rectal Cancer / 대한소화기학회지

We report herein a case of 35-years-old woman in whom portal hypertension (esophageal varix and splenomegaly) developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for rectal cancer. She was transferred for the evaluation of etiology of new-onset portal hypertension. The esophageal varix and splenomegaly were absent before the oxaliplatin based adjuvant chemotherapy. Thorough history taking and serological exam revealed no evidence of chronic liver disease. Liver biopsy was done and there was no cirrhotic nodule formation. Instead, perivenular fibrosis was noted. Considering new development of esophageal varices and splenomegaly after 12 cycles of oxaliplatin-based adjuvant chemotherapy, we could conclude that portal hypertension in this patient were due to sinusoidal injury by oxaliplatin. Finally, we recommend regular follow-up with endoscopy and radiologic examination for checking the development of varices and for screening of varices and splenomegaly in patients with colo-rectal cancer who receive oxaliplatin-based chemotherapy.

A Case of Portal Hypertension after the Treatment of Oxaliplatin Based Adjuvant-Chemotherapy for Rectal Cancer / 대한소화기학회지

We report herein a case of 35-years-old woman in whom portal hypertension (esophageal varix and splenomegaly) developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for rectal cancer. She was transferred for the evaluation of etiology of new-onset portal hypertension. The esophageal varix and splenomegaly were absent before the oxaliplatin based adjuvant chemotherapy. Thorough history taking and serological exam revealed no evidence of chronic liver disease. Liver biopsy was done and there was no cirrhotic nodule formation. Instead, perivenular fibrosis was noted. Considering new development of esophageal varices and splenomegaly after 12 cycles of oxaliplatin-based adjuvant chemotherapy, we could conclude that portal hypertension in this patient were due to sinusoidal injury by oxaliplatin. Finally, we recommend regular follow-up with endoscopy and radiologic examination for checking the development of varices and for screening of varices and splenomegaly in patients with colo-rectal cancer who receive oxaliplatin-based chemotherapy.

Interstitial Lung Disease Associated with Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil, and Leucovorin / 대한소화기학회지

Oxaliplatin with 5-fluorouracil plus leucovorin (FOLFOX) has become the standard treatment in patients with colorectal cancer. Among known toxicities induced by oxaliplatin, hematological, gastrointestinal and neurological toxicities are common. However, acute pulmonary toxicity associated with oxaliplatin is unusual. One case of interstitial lung disease associated with the FOLFOX protocol is reported here.

Interstitial Lung Disease Associated with Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil, and Leucovorin / 대한소화기학회지

Oxaliplatin with 5-fluorouracil plus leucovorin (FOLFOX) has become the standard treatment in patients with colorectal cancer. Among known toxicities induced by oxaliplatin, hematological, gastrointestinal and neurological toxicities are common. However, acute pulmonary toxicity associated with oxaliplatin is unusual. One case of interstitial lung disease associated with the FOLFOX protocol is reported here.

Nuevas alternativas en el tratamiento del cancer gástrico avanzado / Treatment of advanced gastric cancer with oxaliplatin plus 5-fluorouracil/ leucovorin (FOLFOX-4 chemotherapy)

Background: Chemotherapy improves survival in advanced gastric cancer. However the most active combinations have a high level of toxicity that limits their use. Aim: To assess the response, toxicity and survival of patients with advanced gastric cancer, treated with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX-4 chemotherapy). Material and methods: Patients with stage IVgastric cancer, according to the American Joint Committee on Cancer or with relapsed disease and functional capacity 0-2 of the South West Oncology Group, were included. FOLFOX-4 chemotherapy was used as first or second line treatment. The response to treatment and survival were assessed. Results: Between 2003 and 2006, 29 patients (median age 52.5 years, 69 percent males) were treated. FOLFOX-4 was given as first line treatment in 65 percent patients and as second line in 35 percent. There was a complete response in 4.6 percent, partial response in 68 percent, stable disease in 20.6 percent and progression in 6.8 percent. Toxicity was observed in 51 percent of patients, that was hematological and non hematological grade 3/4 in 14 percent. Median survival was 12.5 months. Conclusions: FOLFOX-4 chemotherapy was active in advanced gastric cancer and had a low level of toxicity.