Chronotherapy with 5-fluorouracil, folinic acid and carboplatin for metastatic colorectal cancer; an interesting therapeutic index in a phase II trial

Focan, C.; Kreutz, F.; Focan-Henrard, D; Moeneclaey, N.

doi:10.1016/s0959-8049(99)00282-8

Cited by 18 publications

(15 citation statements)

References 25 publications

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“…There is, however, an important point in common between Granda et al and our studies: The therapeutic index of the combined chemotherapy can be improved by coadministering adriamycin and docetaxel at the times when the most adverse effects are relieved in each drug regardless of differences in study design and dosage. In fact, the availability of combined chronotherapy was reported in few clinical studies (16,34). Thus, we consider that choosing the optimal dosing time for each drug is an essential to yield an excellent therapeutic index for the combination.…”

Section: A(2)-dmentioning

confidence: 99%

Therapeutic Index by Combination of Adriamycin and Docetaxel Depends on Dosing Time in Mice

Tabuchi

Sakaguchi

et al. 2005

Cancer Research

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Although the combination of adriamycin and docetaxel showed a better cure rate against metastatic breast cancer, severe myelosuppression and cardiotoxicity were dose-limiting factors. The purpose of this study was to establish a suitable dosing schedule, based on a chronopharmacologic approach, to relieve severe adverse effects. In experiment 1, adriamycin or docetaxel was injected i.p. at 2, 6, 10, 14, 18, or 22 hours after light onset (HALO) to estimate toxicities. In experiment 2, the dosing time dependency of toxicity and pharmacokinetics were assessed in the combination of adriamycin and docetaxel. In addition, G 2 -M phase in myelocyte cells was determined in nontreated mice. Adverse effects caused by adriamycin were shown to be the worst at 2 HALO and the best at 14 HALO. On the other hand, docetaxel-induced adverse effects were more severe at 14 HALO than at 2 HALO. In the combination study, the D(2)-A(14) group, in which docetaxel was administered at 2 HALO followed by adriamycin at 14 HALO, showed the most toxicity relief of all the treated groups. In the pharmacokinetic study, the dosing time dependency of toxicities was not related to the daily variation of pharmacokinetics of adriamycin and docetaxel. A significant 24-hour rhythm of G 2 -M phase distribution was found in myelocyte cells of nontreated mice. The daily variation of leukopenia caused by docetaxel corresponded to the 24-hour rhythm of G 2 -M phase distribution. These findings reveal that the therapeutic index of the combined chemotherapy can be improved by administering adriamycin and docetaxel at the time when the most adverse effects are relieved in each drug. (Cancer Res 2005; 65(18): 8448-54)

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Section: A(2)-dmentioning

confidence: 99%

Therapeutic Index by Combination of Adriamycin and Docetaxel Depends on Dosing Time in Mice

Tabuchi

Sakaguchi

et al. 2005

Cancer Research

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“…The combination of 5FU, oxaliplatin and leucovorin in accordance with the circadian rhythm gave a higher response rate and fewer complications compared to standard chemotherapy protocols. Focan et al [10] and Shimonov et al [11] have reported that the use of carboplatin instead of oxaliplatin gave the same excellent results of chronotherapy. We decided to evaluate the efficacy, toxicity and quality of life in patients treated by a combined chronotherapy and HAI.…”

Section: Introductionmentioning

confidence: 89%

“…All tumor measurements were done by the same radiologist unaware of the treatment stage. Response was based on standard WHO criteria [10] .…”

Section: Effi Cacy and Toxicitymentioning

confidence: 99%

Combined Systemic Chronotherapy and Hepatic Artery Infusion for the Treatment of Metastatic Colorectal Cancer Confined to the Liver

Shimonov¹,

Hayat

Chaitchik

et al. 2005

Chemotherapy

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Background: The optimal treatment of patients with metastatic colorectal cancer is still a clinical challenge. We describe the use of combined hepatic arterial infusion (HAI) of irinotecan (CPT-11) in conjunction with systemic chronotherapy infusion of 5-fluorouracil (5FU), folinic acid and carboplatin in patients with colorectal liver metastases. Methods: Twenty-three patients with colorectal cancer and isolated liver metastases were enrolled in this trial. Intraoperative insertion of an intra-arterial catheter into the hepatic artery was accomplished during the colon operation (in cases of synchronous tumor) or as a separate procedure in colorectal cancer patients with newly diagnosed liver metastases. A systemic double-lumen double-chamber port was inserted via the subclavian vein as a separate procedure. The treatment plan included irinotecan given by intra-arterial infusion at 150 mg/m² for 1 h. After 2 weeks of rest chronomodulated 5FU (700 mg/m²; peak delivery rate at 04:00 h), leucovorin (175 mg/m²; peak delivery rate at 04:00 h) and carboplatin (40 mg/m²; peak delivery rate at 16:00 h) for 4 days was followed by 10 days’ rest and then given again. After 10 days’ rest another HAI was introduced using the same method. Each cycle of therapy included 2 HAI courses and 2 chronotherapy courses in between. After 2 complete cycles, patients were evaluated for their response with weekly accessed toxicity recording. Results: Seven women, 8 men, median age 61 years (range 46–72). Eight patients had synchronous colon and hepatic disease and 7 patients had metachronous disease. Ten patients had previously been treated with 5FU and leucovorin while 5 patients were chemonaive. The mean number of cycles were 11.6 per patient (range 8–19). Partial response was achieved in 6 patients (40%) and was followed by laparoscopic radiofrequency ablation in 5 patients (33%). Disease stabilization was observed in 2 patients (13%) and disease progression in 7 patients (47%) mainly after previous chemotherapy failure. Side effects were infrequent and mild including grade 2 GIT complaints (5 patients), RUQ pain during HAI (9 patients) and grade 2 hematological complaints in 2 patients. Conclusion: A combined chemotherapy protocol (HAI and chronotherapy) with irinotecan (CPT-11) together with chronomodulated infusion of 5FU, folinic acid and carboplatin can be used in metastatic colorectal patients with a high efficacy rate and minor side effects especially in pretreated patients.

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“…Additional randomized phase II trials comparing chronomodulated administration and constant administration have shown that groups with advanced colorectal cancer subjected to chronomodulated drug infusion had up to a 20% increase in objective response rate, increased tolerance, severely decreased frequencies of dose-limiting toxicity effects, and fewer patients dropping out from treatment when compared to conventional flat-rate infusions (Buroker et al, 1994;Lévi et al, 1994;Focan et al, 2000;Librodo et al, 2012). A meta-analysis performed on five studies comparing these two treatment plans in advanced colorectal cancer showed that chronomodulated drug administration provided a significant increase in overall survival rates while maintaining similar frequencies and intensities of side effects (Liao et al, 2010).…”

Section: Circadian Rhythmicity Of Response To Anticancer Drugsmentioning

confidence: 99%

The contribution of circadian rhythms to cancer formation and mortality

Birky¹,

Bray²

2014

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Cellular circadian clocks represent a coordinated system of gene expression stimulated by both environmental and physiological cues that induces and maintains the rhythmicity of many metabolic processes. Circadian clocks confer the important benefit of anticipation of rhythmic environmental variation which serves to improve the health and survival of the organism. When disruption of these circadian patterns of gene expression occurs due to alterations in the physical (light/dark) and behavioral (feeding/sleeping) environments and/or due to genetic variation in the DNA sequence of clock component and clock regulated genes, negative health consequences can arise. One such consequence appears to be increased risk for cancer development. Circadian disruption has been associated with higher rates of tumorigenesis, faster tumor growth, and increased cancer severity in humans and animal models. Tumor formation is also associated with circadian disruption within the affected cells, and metabolic processes of the cancer host tend to lose their rhythmicity as the cancer becomes more severe. In addition, response to cancer treatment has been shown to have a time-dependent component in certain individuals. Knowledge of the type of circadian disruptions that induce or result from cancer can allow for temporally augmented treatments of cancer, ultimately making cancer treatments more effective and less harmful.

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Chronotherapy with 5-fluorouracil, folinic acid and carboplatin for metastatic colorectal cancer; an interesting therapeutic index in a phase II trial

Cited by 18 publications

References 25 publications

Therapeutic Index by Combination of Adriamycin and Docetaxel Depends on Dosing Time in Mice

Therapeutic Index by Combination of Adriamycin and Docetaxel Depends on Dosing Time in Mice

Combined Systemic Chronotherapy and Hepatic Artery Infusion for the Treatment of Metastatic Colorectal Cancer Confined to the Liver

The contribution of circadian rhythms to cancer formation and mortality

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