Xeroderma pigmentosum group D 751 polymorphism as a predictive factor in resected gastric cancer treated with chemo-radiotherapy

AIM: To evaluate the potential association of xeroderma pigmentosum group D (XPD) codon 751 variant with outcome after chemo-radiotherapy in patients with resected gastric cancer. METHODS: We used PCR-RFLP to evaluate the genetic XPD Lys751Gln polymorphisms in 44 patients with stage III (48%) and IV (20%) gastric cancer treated with surgery following radiation therapy plus 5-fluorouracil/ leucovorin based chemotherapy. RESULTS: Statistical analysis showed that 75% (12 of 16) of relapse patients showed Lys /Lys genotype more frequently (P = 0.042). The Lys polymorphism was an independent predictor of high-risk relapse-free survival from Cox analysis (HR: 3.07, 95% CI: 1.07-8.78, P = 0.036) and Kaplan-Meir test (P = 0.027, log-rank test). CONCLUSION: XPD Lys751Gln polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients

Zdravljenje bolnikov z metastatskim rakom širokega črevesa s fluorouracilom, levkovorinom in interferonom alfa-2a

Based on in viro studies that have demonstrated synergy between fluorouracil (5-FU) and leucovorin (LV) as well as between 5-FU and recombinant alpha-2a interferon (IFN) against colon cancer cell lines a phase II study was carried out to evaluate the toxicity and clinical activity of 5-FU modulated with LV and IFN in patients with metastatic colon cancer. Twenty-two chemotherapy naive patients with measurable metastases of colon cancer have been treated with daily doses of 5-FU 600 mg/m2 in 6-hr intravenous infusion, and of LV 20 mg/m2 intravenously and IFN 6 MU subcutaneously, for 5 days every 4 weeks. Median age was 60 years, median PS (ECOG) was 1 (range 0-2). Liver, soft tissue and lung metastases were found in 12, 5 and 8 patients, respectively. Nineteen patients had a single metastatic site, two double, whereas one had more than two metastatic sites. Patients had 2-9 (mean 5) cycles of treatment.Objective response was observed in 7 patients (32%), and stable disease in 7 patients (32%). Overall median survival was 12.5 months, and for responders 14.4 months. Responses were generally short and median time for progression was 5.5 months. The most frequent adverse reactions were flu-like syndrome (50%), nausea/vomiting (36%), diarhoea (13Č), stomatitis (27%) and leucopenia (13%). This regimen of 5-FU with LV and IFN administration does notappear to be superior to previously published shedules of 5-FU with IFN or 5-FU with LV.Predklinične raziskave so pokazale sinergistični protitumorski učinek fluorouracila (5-FU), levkorina (LV) ter 5-FU in ekombinantnega interferona alfa-2a (IFN). V II. fazi klinične raziskave smo želeli pri bolnikih z metastatskim rakom širokega črevesa ugotoviti toksičnost in učinkovitost zdravljenja s 5-FU, LV in IFN. V raziskavo smo vključili 22 bolnikov z merljivimi zasevki metastatskega raka širokega črevesa. 5-FU smo dajali v 6-urni intravenski infuziji v dnevnem odmerku 600 mg/m2, LV intravensko v dnevnem odmerku 20 mg/m2 in IFN podkožno v dnevnem odmerku 6 MIE. U_inkovine smo dajali 5 dni zapored vsake 4 tedne. Srednja starost bolnikov je bila 60 let. Srednje stanje zmogljivosti (ECOG) je bilo ocenjeno z 1 (rang 0-2). Dvanajst bolnikov je imelo zasevke v jetrih, 5 v mehkih tkivih in 8 v pljučih.Zasevke v enem organu je imelo 19 bolnikov, v dveh organih 2 bolnika in v 3 organih eden. Bolniki so imeli 2 in 9 ciklov zdravljenja, v povprečju 5ciklov. Objektivni odgovor na zdravljenje smo ugotovili pri 7 bolnikih (32%),mirovanje bolezni pri 7 bolnikih (32%). Srednje preživetje je bilo 12,5 meseca, pri bolnikih, ki so odgovorili na zdravljenje pa 14,4 meseca. Odgovorina zdravljenje so bili kratkotrajni in so v povprečju trajali 5,5 meseca. Med neželenimi učinki zdravljenja smo gripozni uotovili pri 50%, slabost in bruhanje pri 36%, drisko pri 13%, stomatitis pri 27% in levkopenijopri 13% bolnikov. Kombinirano zdravljenje s 5-FU, LV in IFN glede na rezultate dosedanjih kliničnih raziskav s 5-FU in LV ali 5-FU in IFN ni bolj učinkovit način zdravljenja

Effect of 5-FU plus leucovorin for adjuvant chemotherapy according to dose related factors in colon cancer

Background : In patients with stage C colon cancer, surgery followed by adjuvant chemotherapy with 5- fluorouracil (5- FU)/ leucovorin (LV) is considered to be the standard treatment. However, the objects of adjuvant therapy and the duration of treatment are still matters of controversy. We investigated the effect of dose related factor(delivered total dose of 5- FU per body square meter, actual dose intensity and relative dose intensity) of the adjuvant 5- FU/ leucovorin regimen on survival in colon cancer. Methods : Of the colon cancer patients with Duke' s B2 and C stage diseases treated with curative resection from December, 1990 to December, 1996, 139 patients treated with 5- FU/LV as an adjuvant chemotherapy were evaluated. The delivered total dose of 5- FU per body square meter, actual dose intensity and relative dose intensity were obtained. The patients were divided into two groups according to the median value of each factor and the survival rates were compared. Results : The total dose of 5- FU administrated per body square meter had a significant effect on the 5- year disease free and overall survival in stage B2 and C colon cancer patients(B2; p=0.025, p=0.045, respectively, C; p=0.011, p=0.0002, respectively). But survival was not affected by the dose intensity. Multivariate analysis demonstrated that only the total dose of 5- FU administrated per body surface area affected the 5- year disease free and overall survival(p=0.0016, p=0.0007, respectively). Conclus ion : It can be concluded that the total dose of 5- FU administered is more important than the DI in adjuvant chemotherapy of colon cancer and the total dose of 5- FU had a significant effect on the survival rate in colon cancer patients. To confirm the total dose effect of 5- FU on survival in this study, multi- institutional, prospective randomized studies should be carried out.(Korean J Med 59:290- 299, 2000)ope

Ergebnisse der chronomodulierten Chemotherapie: eine retrospektive Analyse

Die vorliegende Untersuchung beurteilt die Wirksamkeit und Verträglichkeit einer chronomodulierten Chemotherapie bei 79 Patienten mit metastasierten oder lokal fortgeschrittenen Karzinomen des Kolorektums (n=52), des Pankreas (n=4), der Gallenwege (n=10), des Magens (n=10) sowie bei Einzelfällen anderer Entitäten (n=3) anhand der Bewertung von insgesamt 591 Therapiekursen. Zur Anwendung kamen drei Protokolle einer chronomodulierten Zytostatikaapplikation, deren gemeinsamer Bestandteil die Substanzkombination 5-Fluorouracil/Natriumfolinat war, die jeweils um ein neueres Zytostatikum erweitert wurde: um das Platinderivat Oxaliplatin beim FOLFOX-chrono-Protokoll, um den Topomerase-I-Inhibitor Irinotecan beim FOLFIRI-chrono-Protokoll sowie um das Pyrimidinnucleosidanalogon Gemcitabine beim FOLFGEM-chrono-Protokoll. Als Erfolgsparameter der Therapie wurden Remissionsraten, progressionsfreies Überleben und Nebenwirkungen herangezogen. Die erzielten Ansprechraten und das progressionsfreie Überleben wurden auf Abhängigkeit von einer bereits vorausgegangenen Chemotherapie und der Art des eingesetzten Chronoprotokolls geprüft. Insgesamt waren die Behandlungsergebnisse der chronomodulierten Chemotherapie in der vorliegenden Untersuchung schlechter als die Daten klinischer Studien sowohl zur Chronomodulation als auch zur konventionellen Chemotherapie, wobei sich die Verträglichkeit der Chronomodulation als günstiger erwies

Emerging drugs in colorectal cancer

A raft of novel agents with different modes of action is finally challenging the position of 5-fluorouracil (5-FU) as the gold standard treatment for colorectal cancer. Oral fluoropyrimidines, topoisomerase I inhibitors and new generation platinum compounds are all currently being investigated. There is also increasing interest in the development and use of biological therapies, which may allow treatments to become tailored to individual patients and cause less toxicity than conventional cytotoxics. It is hoped that with the development of these new drugs, the response rates and survival for patients with colorectal cancer will improve from the poor prognosis that many face at present