Analysis of reduced-dose administration of oxaliplatin as adjuvant FOLFOX chemotherapy for colorectal cancer

PURPOSE: An oxaliplatin-based regimen is the most common adjuvant chemotherapy for patients with stage II/III colorectal cancer, but many patients experience dose reduction or early termination of chemotherapy due to side effects. We conducted this study to verify the range of reduction with oncologic safety. METHODS: Patients with stage II/III colorectal cancer who received adjuvant FOLFOX chemotherapy were enrolled in this study. The total amount of oxaliplatin administered per patient was calculated as a percentile based on 12 cycles of full-dose FOLFOX as a standard dose. The cutoff values showing significant differences in survival were calculated, and the clinicopathologic outcomes of patient groups classified by the value were compared. RESULTS: Among a total of 611 patients, there were 107 stage II patients, and 504 stage III patients. At 60% of the standard dose of oxaliplatin, the patients in the dose reduction group were older (62 years vs. 58 years, P = 0.003), had lower body mass index (BMI) (23.1 kg/m2 vs. 24.0 kg/m2, P = 0.005), and were more exposed to neoadjuvant treatment (18.0% vs. 9.1%, P = 0.003) in comparison to the standard group. At 60% of the standard dose, there were no significant differences in 5-year disease-free survival (DFS) and overall survival (OS) between the 2 groups (5-year DFS: 73.5% vs. 74.2%, P = 0.519; 5-year OS: 71.9% vs. 81.5%, P = 0.256, respectively). CONCLUSION: Patients with old age, low BMI, and more frequent exposure to neoadjuvant treatment tended to show lower compliance with chemotherapy. More than 60% dose should be administered to patients with stage II/III colorectal cancer as adjuvant chemotherapy to achieve acceptable oncologic outcomes.

Protective effect of Korean red ginseng on oxaliplatin-mediated splenomegaly in colon cancer

PURPOSE: This study investigated how adding Korean red ginseng extract (KRG) to folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy affected the rate of splenomegaly in colon cancer. METHODS: This retrospective study analyzed 42 patients who were randomly assigned to receive a FOLFOX regimen with or without KRG. Spleen volume change was assessed by computed tomography scans measured before surgery (presurgery volume) and 3 weeks after cessation of the 12th cycle of FOLFOX (postchemotherapy volume). RESULTS: All patients showed increased spleen volume. No difference was observed in median presurgery and postchemotherapy volume between the KRG and control groups. However, a ratio defined as postchemotherapy volume divided by presurgery volume was significantly lower in the KRG group than the control group (median, 1.38 [range, 1.0–2.8] in KRG group vs. median, 1.89 [range, 1.1–3.0] in control group, P = 0.028). When splenomegaly was defined as a >61% increase in spleen volume, the rate of splenomegaly was significantly lower in the KRG group than the control group (28.6% vs. 61.9%, P = 0.03). KRG consumption was inversely associated with developing splenomegaly in multivariate analysis. CONCLUSION: Adding KRG during FOLFOX chemotherapy for colon cancer might protect against oxaliplatin-induced splenomegaly. The protective effect of Korean red ginseng should be investigated with further research.

Quality of life changes during adjuvant chemotherapy in patients with colon cancer

PURPOSE: The survival of advanced colon cancer patients has increased due to the development of surgical techniques and adjuvant chemotherapy. The administration of adjuvant chemotherapy after curative resection is generally accepted as a standard of care. The primary endpoint of chemotherapy should include not only tumor response and survival, but also impact on the quality of life (QoL). We evaluated changes in QoL during adjuvant chemotherapy in patients with colon cancer.METHODS: Between October 2009 and February 2012, 56 patients with stage II and III colon cancer received the combination adjuvant chemotherapy 5-flurouracil/folinic acid with oxaliplatin (FOLFOX). Patients were asked to complete the QoL questionnaire QLQ-C30 version 3 before and after 6 cycles of adjuvant chemotherapy.RESULTS: There was no significant difference in the QoL between the start of chemotherapy and after the completion of 6 cycles. After completion of 6 cycles, global QoL was worse in patients >70 years of age. The functional scale score was low in patients with chemotherapy schedules delayed more than 2 times due to adverse events. Patients with body weight increases greater than 5% scored lower on symptom scales. Interestingly, patients with peripheral neuropathy scored higher on symptom scales.CONCLUSION: QoL changes during adjuvant chemotherapy did not show significant differences. After the sixth chemotherapy, QoL was affected by age, body weight gain, delay of the scheduled chemotherapy, and peripheral neuropathy. Therefore, the proper attitude of physicians focused on reassurance and education of patients is very important during chemotherapy.

Using Pharmacoeconomic Modelling to Determine Value-Based Pricing for New Pharmaceuticals in Malaysia

Background: Decision analysis (DA) is commonly used to perform economic evaluations of new pharmaceuticals. Using multiples of Malaysia’s per capita 2010 gross domestic product (GDP) as the threshold for economic value as suggested by the World Health Organization (WHO), DA was used to estimate a price per dose for bevacizumab, a drug that provides a 1.4-month survival benefit in patients with metastatic colorectal cancer (mCRC). Methods: A decision model was developed to simulate progression-free and overall survival in mCRC patients receiving chemotherapy with and without bevacizumab. Costs for chemotherapy and management of side effects were obtained from public and private hospitals in Malaysia. Utility estimates, measured as quality-adjusted life years (QALYs), were determined by interviewing 24 oncology nurses using the time trade-off technique. The price per dose was then estimated using a target threshold of US$44 400 per QALY gained, which is 3 times the Malaysian per capita GDP. Results: A cost-effective price for bevacizumab could not be determined because the survival benefit provided was insufficient According to the WHO criteria, if the drug was able to improve survival from 1.4 to 3 or 6 months, the price per dose would be $567 and $1258, respectively. Conclusion: The use of decision modelling for estimating drug pricing is a powerful technique to ensure value for money. Such information is of value to drug manufacturers and formulary committees because it facilitates negotiations for value-based pricing in a given jurisdiction.

Adjuvant Chemotherapy Using the FOLFOX Regimen in Colon Cancer

PURPOSE: Great progress has been made in the adjuvant treatment of colon cancer. The aim of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy using the FOLFOX regimen in patients with stage III and high-risk stage II colon cancer. METHODS: Eighty-two patients who underwent a potentially curative resection for stage III or high-risk stage II colon cancer were enrolled in this retrospective study. They received FOLFOX4 or modified FOLFOX6. The primary endpoint was disease-free survival. RESULTS: During the median follow-up of 37 months (range, 21 to 61 months), 14 patients experienced disease relapse. The disease-free survival rate at 3 years was 82.9%: 84.6% for stage II and 82.6% for stage III. At the time of the analysis, 8 patients were dead from recurrence. The probability of overall survival at 5 years was 74.5%: 90% for stage II and 74.6% for stage III. Grade 3 or 4 hematologic adverse events included neutropenia (40.2%), anemia (2.4%), and thrombocytopenia (1.2%). Gastrointestinal toxicities included grade 3 or 4 nausea (4.9%) and stomatitis (2.4%). Peripheral sensory neuropathy was observed in 81.7% of the patients during treatment. Of the 11 patients (13.4%) who had grade 3 peripheral sensory neuropathy during treatment, grade 3 symptoms were persistent in 3 patients with gait disturbance at the time of analysis. No treatment-related deaths were recorded. CONCLUSION: Postoperative chemotherapy using the FOLFOX regimen, oxaliplatin in combination with 5-fluorouracil and leucovorin, is effective and tolerable in patients with stage III and high-risk stage II colon cancer.

Tingling Sensation and Difficulty in Daily Living of Clients Treated FOLFOX Chemotherapy after Colon Resection / 재활간호학회지

PURPOSE: This study was to investigate difficulties in daily activities and tingling from patients having treatment of FOLFOX chemotherapy after colon resection. METHOD: This study included 103 patients hospitalized for FOLFOX chemotherapy in one of the university affiliated hospital from August 1, 2008 through September 30, 2009. Data were collected using the questionnaire comprised general symptoms, tingling, difficulties in daily activities and coping behavior. Using the SPSS 14.0 program, data analytic methods include Chi-Square test, ANOVA, Scheffe's test. RESULTS: The tingling sensation occurred in hands, feet, mouth, throat. Contacts with cold objects and the number of chemotherapy cycle worsen tingling sensation. Patients experienced difficulties in daily activities such as personal hygiene, kitchen work, eating cold food, sleeping cold, using fine motors like button up, writing, or using knife. The coping behavior included drinking warm water, sleeping warm, using gloves and socks, wearing comfortable shoes, massaging hands and getting help from supporters. CONCLUSION: An educational guideline for promoting coping behavior to relieve tingling sensation and difficulty in daily living in patients with FOLFOX chemotherapy is needed.

Reduced Dose Intensity FOLFOX-4 as First Line Palliative Chemotherapy in Elderly Patients with Advanced Colorectal Cancer

To evaluate the toxicity and efficacy of a reduced dose intensity (mini-) FOLFOX-4 regimen as a first-line palliative chemotherapy in elderly patients (> or =70 yr of age) with advanced colorectal cancer, data from prospective databases at Seoul National University Bundang Hospital and Seoul Municipal Boramae Hospital were analyzed. A total of 20 patients were enrolled between January 2001 and August 2004, and were treated with oxaliplatin 65 mg/m2 on day 1, and with 2-hr infusions of leucovorin 150 mg/m2 followed by a 5-FU bolus (300 mg/m2) and 22-hr continuous infusions (450 mg/m2) for 2 consecutive days every 2 weeks until progression, unacceptable toxicity or patient refusal. Sixteen patients were evaluable for response with an overall response rate of 43.8%. Median progression-free survival was 4.8 months (95% CI: 3.0-6.7) and overall survival was 13.5 months (95% CI: 11.1-16.0). The main side effects were anemia and neutropenia, which were observed in 20.8% and 17.7%, respectively, of the total cycles administered. There were no grade 4 toxicities and only one patient suffered from febrile neutropenia. No grade 3 toxicities occurred except for anemia (5.2%) and vomiting (1.0%). In conclusion, the mini-FOLFOX-4 regimen was found to be well tolerated with acceptable toxicity, and to provide a benefit for elderly patients with colorectal cancer.