Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer

Rosati, Gerardo; Rossi, Antonio; Tucci, A.; Pizza, C.; Manzione, Luigi

doi:10.1023/a:1011115207518

Cited by 11 publications

(10 citation statements)

References 17 publications

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“…We found evidence that our regimen decreases the specific drug neurotoxicity. Possible sources of reduced neurotoxicity include the weekly schedule developed by our group and confirmed by other studies with the same reduced toxicity [16,17,18]and a lower L-OHP dosage for single administration. Only 2 patients experienced grade 3 myelotoxicity.…”

Section: Discussionsupporting

confidence: 63%

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Phase II Trial of Oxaliplatin and Tegafur/Uracil and Oral Folinic Acid for Advanced or Metastatic Colorectal Cancer in Elderly Patients

Rosati

Cordio²,

Tucci³

et al. 2005

Oncology

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Objectives: Colorectal cancer is usually diagnosed in elderly patients. Since there is clear evidence that such patients are under-treated and under-represented or even excluded from clinical studies and there are no reliable and prospective data on the feasibility and efficacy of an oxaliplatin (L-OHP)-based chemotherapy in this setting, we have tested the L-OHP plus oral uracil/tegafur (UFT) and oral folinic acid (FA) combination as first-line therapy in patients with advanced or metastatic colorectal cancer (MCRC) aged 70 or older. Patients and Methods: Forty-seven patients with advanced or MCRC, aged over 70, were treated with L-OHP 65 mg/m² as an intravenous 3-hour infusion on day 1 and 8 plus UFT 300 mg/m² and FA 90 mg in 3 divided doses given orally on days 1–14 for each 3-week cycle. Patients were followed by a geriatric and a quality of life (QoL) assessment with specific scales and EORTC-QLQ-C30 questionnaire. Results: All patients were assessable for toxicity and 45 for response to treatment. Complete response was achieved in 2 patients (4%) and partial response in 22 (47%) [overall response rate, 51%; 95% confidence interval (CI): 40.7–61.2%]; 18 patients (38%) had stable disease, and 5 (11%) had disease progression. The median duration of response was 8 months (range, 3–19+ months). After a minimum follow-up of 17 months, the median time to disease progression and the median overall survival were 8.0 (95% CI: 6.7–9.3%) and 14.1 (95% CI: 11.0–17.1%) months, respectively. Regimen safety was manageable. Most adverse events were mild to moderate, and this did not result in QoL impairment. The most common grade 3–4 treatment-related adverse events were diarrhea (17%), neutro- and thrombocytopenia (2%), laryngeal spasm (2%), and peripheral neuropathy (12.7%). No treatment-related deaths occurred. Conclusions: These results confirmed that this tested chemotherapy combination is active with acceptable tolerability and QoL maintenance in elderly patients with advanced or MCRC.

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Section: Discussionsupporting

confidence: 63%

“…After taking into account its reduced neurotoxicity in the weekly schedule [16,17,18],we preferred an L-OHP subdivision dosage at 65 mg/m 2 for single administration. The secondary aims were to evaluate the treatment in terms of time to disease progression (TTP), overall survival (OS), and QoL.…”

Section: Introductionmentioning

confidence: 99%

Phase II Trial of Oxaliplatin and Tegafur/Uracil and Oral Folinic Acid for Advanced or Metastatic Colorectal Cancer in Elderly Patients

Rosati

Cordio²,

Tucci³

et al. 2005

Oncology

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“…Typically, the disease leads to the formation of plaques and lesions in various areas of the brain and the spinal cord. MS predominately affects people of temperate latitudes in the Western hemisphere, and its prevalence, depending on the different countries, ranges from 4 to 248 per 100,000 (1). About two million people worldwide suffer from MS, and it remains one of the leading causes of disability in young adults.…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Potential of HDAC Inhibitors in the Treatment of Multiple Sclerosis

Faraco

Cavone

Chiarugi

2011

Mol Med

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Multiple sclerosis (MS) is a devastating autoimmune disorder of the central nervous system (CNS) for which there is no efficacious cure. Thanks to numerous preclinical and clinical studies, drugs able to mitigate the inexorable course of the disease have been made available recently. Still, there is a terrible need for compounds capable of reducing the severity of the autoimmune attack and of blocking progression of the disorder. Also, besides the classic immunosuppressive strategies, it is now appreciated that compounds directly targeting neuronal death can be of relevance to the treatment of MS patients. Acetylation homeostasis is a key regulator of both immune cell activation and neuronal survival. Of note, potent histone deacetylase inhibitors (HDACi) endowed with antiinflammatory and neuroprotective properties have been identified. Efficacy of HDACi in experimental models of MS has been reported consistently. In this review, we provide an appraisal of the literature on HDACi and MS, also discussing the mechanisms by which HDACi can suppress the autoimmune attack to the CNS.

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“…Oxaliplatin is traditionally administered by a 2-hour infusion. However, it was demonstrated that a continuous infusion of oxaliplatin (4–12 h) is feasible, because pharmacokinetic profiles are similar to those profiles registered after chronomodulated infusion [20,21,22,23,24,25]. We decided to use continuous infusion of oxaliplatin with the aim to maximize the clinical efficacy infusing the drug during its higher cytotoxic efficacy hours.…”

Section: Introductionmentioning

confidence: 99%

“…We decided to use continuous infusion of oxaliplatin with the aim to maximize the clinical efficacy infusing the drug during its higher cytotoxic efficacy hours. Few studies demonstrated that the weekly administration of oxaliplatin is feasible with a high clinical efficacy and a good toxicity profile compared with the biweekly or three-weekly schedules [25,26,27]. …”

Section: Introductionmentioning

confidence: 99%

Continuous Infusion of Oxaliplatin plus Chronomodulated Capecitabine in 5-Fluorouracil- and Irinotecan-Resistant Advanced Colorectal Cancer Patients

Santini

Vincenzi²,

Cesa³

et al. 2005

Oncology

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Objectives: The aim of the study was to define the feasibility and efficacy of Xelox (capecitabine and oxaliplatin) administered through a new and original schedule in advanced pretreated colorectal cancer (CRC) patients. Methods: 36 metastatic CRC patients resistant at least to a previous 5-fluorouracil- and irinotecan-based chemotherapy line were included in the study. Treatment: Oxaliplatin 70 mg/m² as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on days 1, 8 plus chronomodulated capecitabine 1,750 mg/m²/day per os (8.00 a.m. 25% of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on days 1–14 every 21 days. 16 (44.4%) patients had previously received only 1 chemotherapy line for metastatic disease and 20 patients (55.6%) 2 chemotherapy lines. Moreover, 12 patients (33.3%) progressed after a first or second line of oxaliplatin-based regimen as well. Results: Most frequent related G3–4 adverse reactions were diarrhea (11.6%), nausea/vomiting (8.3%), neuropathy (8.3%), mucositis (8.3%), asthenia (16.7%) and hand-foot syndrome (5.5%). G3–4 anemia, leucopenia and liver toxicities were not observed. The overall response rate was 30.6% (11/36 patients). Disease stabilization was observed in 13 patients (36.1%) and progression in 12 patients (34.3%). Between the 12 oxaliplatin-resistant patients, the overall response rate was 25% (3 patients); 6 patients (54.5%) obtained a stable disease, and only 3 patients (25%) progressed. The median overall survival was 11.3 months (95% confidence interval 7.0–15.7 months), the median response duration 2.8 months (95% confidence interval 1.2–5.6 months) and the median time to progression 6.7 months (95% confidence interval 5.7–6.3 months). The 1-year survival rate was 53.8%. Conclusions: The high overall tumor growth control, the remarkable median time to progression and overall survival and the good safety profile are of particular interest for patients with heavy pretreated metastatic CRC.

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Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer

Cited by 11 publications

References 17 publications

Phase II Trial of Oxaliplatin and Tegafur/Uracil and Oral Folinic Acid for Advanced or Metastatic Colorectal Cancer in Elderly Patients

Phase II Trial of Oxaliplatin and Tegafur/Uracil and Oral Folinic Acid for Advanced or Metastatic Colorectal Cancer in Elderly Patients

The Therapeutic Potential of HDAC Inhibitors in the Treatment of Multiple Sclerosis

Continuous Infusion of Oxaliplatin plus Chronomodulated Capecitabine in 5-Fluorouracil- and Irinotecan-Resistant Advanced Colorectal Cancer Patients

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