Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

Bécouarn, Y.; Ychou, Marc; Ducreux, Michel; Borel, Christian; Bertheault-Cvitkovic, F.; Seitz, Jean‐François; Nasca, S; Nguyen, T.D.; Paillot, B; Raoul, Jean‐Luc; Duffour, Jacqueline; Fandi, A.; Dupont-André, Ghislaine; Rougier, Philippe

doi:10.1200/jco.1998.16.8.2739

Cited by 265 publications

(106 citation statements)

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“…In the past debulking surgery accompanied by systemic pH incompatibility 5FU cannot be mixed with OX for intraperitoneal use [17,18] . Despite its advantageous phar macokinetic properties MMCinduced leukopenia due to bone marrow toxicity after HIPEC is a known and frequently encountered sideeffect of this treatment [19] .…”

Section: Discussionmentioning

confidence: 99%

“…The phenomenon of female gender being associated with a greater risk for chemotherapy induced leukopenia has been reported previously, but its reasons are still unknown. Bécouarn et al [17] provide an explanation for the association between leukopenia and female gender. The authors speculate that women harbor a relatively large surface area of the peritoneum combined with a smaller plasma volume as compared with men of equal weight [22] .…”

Section: Discussionmentioning

confidence: 99%

“…As far as this is concerned the literature presents controversial results. Bécouarn et al [17] found a higher, although not significant, incidence of neutropenia in the splenectomized patients after MMCHIPEC, whereas Bidus et al [24] reported also a potentially protective effect of splenectomy on leukopenia in patients receiving adjuvant systemic chemotherapy. The time when chemotherapy was administered could be the decisive variable for these conflicting results.…”

Section: Peer-reviewmentioning

confidence: 96%

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Incidence of leukopenia after intraperitonealvscombined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei

Horvath¹,

Beckert²,

Struller³

et al. 2016

WJGPT

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AIM:To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy (HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared. METHODS:Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort (n = 32) received Mitomycin C (MMC)-based HIPEC intraperitoneally (35 mg/m² for 90 min) and the second cohort (n = 10) received a bidirectional therapy consisting of oxaliplatin (OX) (300 mg/m 2 for 30 min) intraperitoneally and 5-fluorouracil (5-FU) 400 mg/m² plus folinic acid 20 mg/m² intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC (completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery (CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as < 4000 cells/m³. RESULTS:Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group (10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients (33%) required medical treatment. Patients affected by leukopenia were predominantly female (7/10 patients) and older than 50 years (8/10 patients Author contributions: Horvath P designed and performed the research and wrote the paper; Beckert S performed the statistical analysis and supervised the report; Struller F contributed to the research; Königsrainer A supervised the report; Königsrainer I interpreted the data, supervised the report and made the final revision of the paper.Institutional review board statement: We confirm that retrospective data collection and dealing with personal data was conducted in accordance to the guidelines of the local ethics committee. Informed consent statement:We confirm that all patients gave written or oral informed consent prior to their inclusion. Conflict-of-interest statement:We declare that we have no conflict of interest. Data sharing statement: No additional data are available.Open-Access: This article is an openaccess article which was selected by an inhouse editor and fully peerreviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: http://creativecommons.org/ licenses/bync/4.0/ CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMCbased HIPEC protocols primarily affecting females and older patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Peer-reviewmentioning

confidence: 96%

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Incidence of leukopenia after intraperitonealvscombined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei

Horvath¹,

Beckert²,

Struller³

et al. 2016

WJGPT

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“…In the US there are almost 100 000 new cases and almost 50 000 deaths each year. 5-Fluorouracil (5-FU) is one of the cytostatic agents that, as a single agent (but in combination with folinic acid), produces response rates averaging 20% (Skibber et al, 2000); irinotecan, raltitrexed and oxaliplatin have in some studies achieved similar response rates (Cunningham et al, 1995;Becouarn et al, 1998;Diaz-Rubio et al, 1998;Saltz et al, 2000). 5-Fluorouracil leads to a modest survival benefit when compared to approaches such as best supportive care (Nodic Gastrointestinal Tumor Adjuvant Therapy Group, 1992;Allen-Mersh et al, 1994;Hafstrom et al, 1994).…”

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confidence: 99%

EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer

et al. 2003

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Cancer of the colon and rectum is one of the most frequent malignancies both in the US and Europe. Standard palliative therapy is based on 5-fluorouracil/folinic acid combinations, with or without oxaliplatin or irinotecan, given intravenously. Oral medication has the advantage of greater patient convenience and acceptance and potential cost savings. S-1 is a new oral fluorinated pyrimidine derivative. In a nonrandomised phase II study, patients with advanced/metastatic colorectal cancer were treated with S-1 at 40 mg m À2 b.i.d. for 28 consecutive days, repeated every 5 weeks, but by amendment the dose was reduced to 35 mg m À2 during the study because of a higher than expected number of severe adverse drug reactions. In total 47 patients with colorectal cancer were included. In the 37 evaluable patients there were nine partial responses (24%), 17 stable diseases (46%) and 11 patients had progressive disease (30%). Diarrhoea occurred frequently and was often severe: in the 40 and 35 mg m À2 group, respectively, 38 and 35% of the patients experienced grade 3 -4 diarrhoea. The other toxicities were limited and manageable. S-1 is active in advanced colorectal cancer, but in order to establish a safer dose the drug should be subject to further investigations.

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“…1,2 Combinations of high dose continuous 5 fluorouracil (5FU) and folinic acid are among the most active regimens. More recently, the third generation platinate oxaliplatin has shown significant activity, both as a single drug [3][4][5][6] and in combination with fluorouracil. 7,8 Oxaliplatin containing regimens are now considered standard therapeutic options for metastatic CRC patients.…”

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confidence: 99%

Lhermitte sign and urinary retention

Taieb

Trillet‐Lenoir

Rambaud

et al. 2002

Cancer

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BACKGROUNDRegimens combining oxaliplatin with fluorouracil and folinic acid are standard therapeutic options for patients with metastatic colorectal carcinoma. Oxaliplatin has a good safety profile, although it is responsible for dose‐limiting neurotoxicity typically consisting of two distinct clusters of symptoms. Cold‐induced distal paresthesiae occur during or shortly after infusion in most patients and are usually transient and mild. A persistent sensory peripheral neuropathy may develop with prolonged treatment, eventually causing superficial and deep sensory loss, sensory ataxia and functional impairment.METHODSThe authors report four cases of atypical neurotoxicity induced by oxaliplatin in patients treated for metastatic colorectal carcinoma. Two patients were male and two were female, with an age range of 52–59 years.RESULTSThree patients experienced Lhermitte sign and two experienced urinary retention. In all cases, the cumulative dose of oxaliplatin was higher than 1000 mg (range, 1248–2040 mg). Brain and spinal magnetic resonance imaging was performed in two patients and was normal. Somatosensory evoked potentials were recorded in two patients and suggested cervical dorsal column dysfunction. Symptoms resolved a few weeks after discontinuation of oxaliplatin.CONCLUSIONSLhermitte sign may be induced via a neurotoxic effect on the ascending axons of these T‐shaped neurons. An atonic bladder may be the result of damage to the sensory portion of the sacral reflex arc, either in the dorsal roots, as for example in diabetic neuropathy, or in the posterior columns, as in tabes dorsalis. Alternatively, it may result from a paralysis of the parasympathetic fibers that control the bladder musculature. It is unclear at present whether the micturition difficulties observed in patients in the current series are due to sensory neuropathy or to autonomic neuropathy, event if the former hypothesis seems more likely, as autonomic neuropathy has not been previously observed with oxaliplatin, and its association with cisplatin is exceedingly rare and controversial. Cancer 2002;94:2434–40. © 2002 American Cancer Society.DOI 10.1002/cncr.10500

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Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

Abstract: This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.

Cited by 265 publications

References 15 publications

Incidence of leukopenia after intraperitonealvscombined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei

Incidence of leukopenia after intraperitonealvscombined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei

EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer

Lhermitte sign and urinary retention

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