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PubMed1990

Azidothymidine inhibition of thymidine kinase and synergistic cytotoxicity with methotrexate and 5-fluorouracil in rat hepatoma and human colon cancer cells.

Azidothymidine (AZT, 3'-azido-3'-deoxythymidine, zidovudine) competitively inhibited the activity of thymidine kinase (EC 2.7.1.21) in extracts of rat hepatoma and sarcoma cells; Dixon plots yielded a Ki = 1-2 microM. Azidothymidine (100 microM) exerted synergistic cytotoxicity with methotrexate (0.05 microM) in hepatoma cells in culture in clonogenic assay. Thymidine (50 microM) counteracted the effect of azidothymidine and prevented synergistic action. Azidothymidine (10 microM) was synergistically cytotoxic with 5-fluorouracil (0.3 and 0.5 microM) in HT-29 human colon carcinoma cells. Thymidine (10 microM) abolished synergism. These studies suggest a new role for azidothymidine which, as an inhibitor of thymidine salvage, should enhance synergistically the clinical anticancer impact of blockers of de novo biosynthesis of thymidylates (methotrexate, 5-fluorouracil).

Animals↗

PubMed1991

AZT: a biochemical response modifier of methotrexate and 5-fluorouracil cytotoxicity in human ovarian and pancreatic carcinoma cells.

In ovarian and pancreatic carcinoma cell lines, the activity of the salvage enzyme, thymidine kinase (EC 2.7.1.21), was 2- to 13-fold higher than that of the key enzyme of thymidylate de novo biosynthesis, thymidylate synthase (dTMP synthase, EC 2.1.1.45). AZT (3'-azido-3'-deoxythymidine, zidovudine) competitively inhibited thymidine kinase activity in extracts of human ovarian and pancreatic carcinoma cells, with Dixon plots yielding Ki = 1.1 microM in both cell lines. AZT (20 microM) yielded synergistic cytotoxicity with methotrexate (0.4 microM) in human pancreatic carcinoma cells in clonogenic assay and also with methotrexate (0.02 microM) in human ovarian carcinoma cells, as measured by cell counts. Thymidine (10 microM) and hypoxanthine (100 microM) reversed these inhibitions. AZT (20 or 40 microM) also provided synergistic cytotoxicity with 5-fluorouracil (0.5 and 1.0 microM) in human pancreatic carcinoma cells in clonogenic assay. These studies suggest a new role for AZT, which, as an inhibitor of thymidine salvage, should be useful as a biochemical response modifier to provide a synergistic clinical anticancer impact on de novo biosynthesis of thymidylates in conjunction with methotrexate or 5-fluorouracil.

Animals↗

PubMed2006

Inhibition of human gastric carcinoma cell growth by atofluding derivative N3-o-toluyl-fluorouracil.

AIM: To evaluate the growth inhibition efficacy of atofluding derivative N3-o-toluyl-fluorouracil (TFU) on human gastric carcinoma cell lines SGC-7901 and MKN-45. METHODS: Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo. RESULTS: TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In vivo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally well tolerated by mice with less than 20% reduction in body weight. CONCLUSION: TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil (5-FU) mediated by the enzymes.

Animals↗

PubMed1983

Whole body autoradiography of 5-fluorouracil-6-14C in nude mice bearing murine leukemia cells P388.

Whole body autoradiography of 5-fluorouracil (5-FU)-6-14C intraperitoneally injected to nude mice bearing murine leukemia cells (P388) indicated that absorption of 5-FU from mesenterium to digestive gland and canals was so quick that liver and stomach as well as duodenum had intensive radioactivity as 10 and 30 min after administration. Lower intestine had less radioactivity than duodenum and it was reduced noticeably as time passed. The activity in the kidney at initial stage was distributed throughout the cortex but it was concentrated to transitional zone between cortex and outer medulla at h stage. Lung had moderate activity throughout this experiment. Muscles and central nervous system had little radioactivity. Bone appeared radioactive to some extent. Interestingly, heart and cross section of blood vessels in liver and kidney had not radioactivity indicating that 5-FU was not retained in circulating system. These results were compared with that of uracil-14C and 5-fluorouracil-2-14C described by others.

Animals↗

PubMedDate not supplied

Analysis of recovery time indexes in 5-fluorouracil-treated cancer patients.

Based on our previous experience in doxorubicin-treated patients, in whom we observed a significant increase of ventricular recovery time indexes, we analyzed these non- invasive parameters of myocardium electrical instability in forty-three 5-fluorouracil-treated patients, to test the hypothesis of a mechanoelectrical disarrangement occurring in 5-fluorouracil (5FU) cardiotoxicity. All patients enrolled were studied at the first presentation and following chemotherapy. The study showed the absence of any significant changes in recovery time indexes or in other electrocardiographic parameters. Our data suggest that 5FU does not interfere with electrical properties of myocardial fibers.

Aged↗

PubMedDate not supplied

Hepatic arterial infusion chemotherapy with continuous low dose administration of cisplatin and 5-fluorouracil for multiple recurrence of hepatocellular carcinoma after surgical treatment.

To date, conventional treatments for multiple intrahepatic recurrence of hepatocellular carcinoma (HCC) after surgery are unsuccessful. The aim of this retrospective study was to evaluate the prognostic effectiveness of a new infusion chemotherapy of cisplatin (CDDP) and 5-fluorouracil (5-FU) via hepatic artery for HCC with multiple intrahepatic recurrence. Fifty-two patients, who had postoperative multiple recurrence of HCC (more than 3 tumors), were enrolled in this study. Thirty-one patients were treated by hepatic arterial infusion chemotherapy via a subcutaneously implanted injection port. A one-week course of this treatment consisted of daily administration of cisplatin (10 mg for 1 h on days 1-5) and subsequent daily administration of 5-fluorouracil (250 mg for 5 h on days 1-5). Three to six sequential one-week courses were performed (the CDDP,5-FU group). Twenty-one patients underwent conventional interventional therapies including transcatheter arterial chemoembolization, lipiodolization (the conventional group). The complete response rate and the effective response rate in the CDDP,5-FU group were 29.0% and 71.0%, respectively. The 5-year survival rate in this group was 45.7%, which was significantly better than that in the conventional group. Based on multivariate analysis, CDDP,5-FU hepatic arterial infusion chemotherapy was found to be significant in prolonging survival, and this treatment achieved favorable therapeutic results for multiple recurrence of HCC. As part of a multidisciplinary approach this treatment is expected to improve the prognosis of patients with advanced HCC.

Adult↗

PubMedDate not supplied

Cisplatin, mitomycin-C, 5-fluorouracil and leucovorin combination chemotherapy (l-FCM) in locally advanced unresectable or metastatic gastric carcinoma: a phase-II study.

Despite relevant progress, the impact of chemotherapy on advanced gastric cancer patients' survival is still unsatisfactory. Thus, the key objective of our efforts should be palliation of the symptoms and the maintenance of an adequate quality of life. In this phase-II study, we evaluated toxicity and efficacy of the combination of cisplatin, fluorofolates and mitomycin C. Thirty-one advanced gastric cancer patients received cisplatin (15 mg/m2) and 5-fluorouracil (350 mg/m2), both for 5 consecutive days every 4 weeks; 5-fluorouracil infusion was preceded by a rapid i.v. injection of 100 mg/m2 leucovorin, while mitomycin-C (10 mg/m2) was administered on day 1 of odd cycles. Cycles were repeated every 4 weeks until disease progression. We recorded 16 objective responses (51.6%, 95% confidence interval: 42.63-60.57); furthermore, such a response rate was coupled with a moderate degree of toxicity and an extremely good tolerance. In particular, alopecia, a frequent and distressing side-effect in patients, especially women, in our series occurred only in two patients. This treatment appears to be an active and tolerable therapeutic option for patients with advanced gastric carcinoma.

Adult↗

PubMed1990

Electrocardiographic changes simulating acute myocardial infarction or ischemia associated with combination chemotherapy with etoposide, cisplatin, and 5-fluorouracil.

Three cases of cardiotoxicity manifested by chest pain, tachycardia, respiratory distress, and electrocardiographic changes simulating acute myocardial infarction or ischemia were observed during the course of combination chemotherapy with etoposide, cisplatin, and continuous infusion of 5-fluorouracil in patients with advanced non-small cell lung cancer. There was no cardiac enzyme elevation. A similar but rare clinical syndrome has been described in association with 5-fluorouracil infusion as a single agent or in combination with other chemotherapeutic agents. We describe the cases and review their possible pathogeneses and clinical implications.

Adult↗

PubMed1997

A randomized trial comparing cisplatin plus 5-fluorouracil with or without levamisole in operable gastric cancer.

OBJECTIVES: To determine the effectiveness and toxicity when levamisole was added to the adjuvant combination chemotherapy in patients with operable gastric cancer. METHODS: After en bloc resection of gastric cancer without gross or microscopic evidence of residual disease from April 1991 to December 1992, 100 patients were randomized to 6 months of 5-fluorouracil 1,000 mg/m2/day administered as continuous infusion for 5 days, cisplatin 60 mg/m2/day as intravenous infusion for 1 day with or without levamisole (50 mg every eight hours P.O for a period of three days every 2 weeks for 6 months). This chemotherapy treatment was begun within 2 to 4 weeks after the surgery. The chemotherapy consisted of discrete 5-day courses administered at 4-weeks intervals. All 100 patients are assessable. RESULTS: The fifty patients were assigned to each treatment group. There was no statistical difference and no bias in the distribution of characteristics of the 100 evaluable patients between the two groups. A total of 274 courses of treatment were given in the levamisole group and 260 courses of treatment in non-levamisole group. Eleven patients in each group did not finish planned 6 courses of treatment mainly due to non-compliance. At median follow up of 39 months, 32 patients relapsed 19 in the levamisole group and 13 in the non-levamisole group (p = 0.284). Twenty five patients died of relapsed diseases, 15 in the levamisole group and 10 in the non-levamisole group. The levamisole group tended to show more risk of overall death rate and recurrence than the non-levamisole group. However, this result was not statistically significant at 3 years. The treatment was well tolerated in both treatment groups. The grade 2-3 toxicities were nausea/ vomiting (levamisole, non-levamisole group; 31.7%, 29.3% of treatment courses respectively), diarrhea (7.6%, 8.4%), mucositis (11.6%, 12.3%), and leukopenia (9.8%, 9.6%). CONCLUSION: Levamisole had negative effects on disease-free survival and overall survival when added to adjuvant combination chemotherapy of cisplatin and 5-fluorouracil in patients with operable gastric cancer. Both treatment arms were generally well tolerated and the toxicity profile was similar with or without levamisole.

Adjuvants, Immunologic↗

PubMedDate not supplied

5-Fluorouracil reduces scarring after strabismus surgery.

PURPOSE: To examine the effect of topically administered 5-fluorouracil during strabismus surgery on post-operative scarring and the strength of the tendon-muscle union. METHODS: Bilateral superior and inferior rectus muscle recessions were performed on 10 Stauffland white rabbits. The operated muscles in one eye received a 5-min topical application of 50 mg/mL solution of 5-fluorouracil (5-FU). The fellow eye received placebo treatment with a 5-min application of balanced sterile saline. Both eyes were enucleated 29 days postoperatively and examined for evidence of scarring. The tensile strength of both treated and untreated muscles was measured. Two additional rabbits received no surgery but had their eyes enucleated to serve as controls for tensile strength measurements. RESULTS: A significant reduction (P = 0.0001) in the amount of scarring was noted in eyes treated with 5-FU. A reduction in the tensile strength of both operated groups compared with the unoperated groups (P = 2.72 x 10(-12)) was noted, with a small but significant difference between the two operated groups (P = 0.0423). CONCLUSION: This study suggests that 5-FU may be a useful adjunctive therapy in strabismus surgery, especially when extensive postoperative scarring is expected.

Administration, Topical↗

PubMedDate not supplied

Combined effect of polytetrafluoroethylene and 5-fluorouracil on delayed adjustable strabismus surgery.

PURPOSE: To determine a more reliable method for performing delayed suture adjustment to prevent the formation of postoperative adhesions and delay the time of adjustment. METHODS: Thirty-two rabbit eyes were divided into three groups. After recession of the superior rectus muscle, 5-fluorouracil (5-FU) was administered beneath and over the superior rectus muscle in group 5-FU (12 eyes); polytetrafluoroethylene (PTFE) and 5-FU were administered in group P-f (10 eyes); and PTFE, 5-FU, and Viscoat (chondroitin sulfate, sodium hyaluronate, Alcon Laboratories Inc, Fort Worth, Tex) were administered in group P-fv (10 eyes). Delayed adjustment was performed once on each superior rectus muscle at 1, 2, and 3 weeks postoperatively in group 5-FU and at 2 and 4 weeks postoperatively in groups P-f and P-fv. The length and force for the adjustment and the degree of adhesions were recorded. RESULTS: The use of fluorouracil allowed adjustment to be delayed up to 1 week after surgery in three of four eyes. The combined use of PTFE and 5-FU or addition of Viscoat allowed adjustment to be delayed for up to 4 weeks after surgery in four of five eyes. CONCLUSION: The combined use of PTFE, 5-FU and Viscoat is useful for delaying suture adjustment in rabbit eyes.

Animals↗

PubMed1993

A cost-utility approach to the use of 5-fluorouracil and levamisole as adjuvant chemotherapy for Dukes' C colonic carcinoma.

OBJECTIVE: To perform an economic evaluation of the joint use of 5-fluorouracil and levamisole as adjuvant chemotherapy in patients with fully resected Dukes' Stage C carcinoma of the colon, compared with resection and no chemotherapy. The evaluation was prompted by a study (N Engl J Med 1990; 322: 352-358) which recommended a new treatment standard for colon cancer: a 52-week course of fluorouracil, with levamisole every second week, as adjuvant chemotherapy. This recommendation raised several concerns, particularly about the quality of life of patients undergoing such a long course of chemotherapy and the costs to the health care system. METHODS: The cost of the surgery plus chemotherapy was estimated and compared with the cost of surgery alone. Descriptions of quality of life were developed from interviews with patients and health professionals, and the time trade off technique was then used to derive utility weights from a small sample (16) which were used to adjust length of life to reflect quality, in terms of a "quality adjusted life year" (QALY). RESULTS: Chemotherapy increases the total cost of treating a patient with colon cancer by $7000, from $6000 to $13,000. Incorporating quality of life reduced the extra benefit gained from the chemotherapy from 2.4 life years to 0.4 QALYs. Thus the result is a cost of $17,500 to achieve an extra QALY from this particular treatment. CONCLUSIONS: The results of this analysis are only tentative, as the quality of life descriptions were not measured over time but from a cross-sectional survey of patients, and the valuations of health states were derived from a small sample. However, we believe them to be indicative, and conclude that it is perhaps more appropriate for the use of chemotherapy to be an option rather than standard treatment until further research on these aspects is complete.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

[Combination therapy of daily intramuscular injection of interferon-alpha and oral administration of fluorouracil for advanced renal cell carcinoma].

BACKGROUND: To achieve optimum drug delivery of Interferon-alpha in treatment of renal cell carcinoma, a regimen consisting of its daily intramuscular administration, in combination with oral fluorouracil, was designed and carried out. Its efficacy is examined retrospectively. METHODS: In our department 7 patients with disseminated renal cell carcinoma were treated with daily intramuscular injection of interferon-alpha (3 x 10(6) IU) and daily oral administration of fluorouracil. All patient was nehprectomized before initiation of the regimen. RESULTS: Two patients achieved complete, and three patients achieved partial response radiographically (Overall response rate 71%). Metastatic sites of responders were lung (4) and pleura (2). The time required until response was 3.9 (median 5.4) months. In two responders, new lesions appeared in other organs despite durable response in initial pulmonary metastatic sites. There were two no-responders, one patient is alive with stable disease and the other patient died for progression of the disease. In all, two patients died of disease, one died for other cause, one surviving without evidence of disease, and three are surviving with disease. No significant side effect was noted in these seven patients. CONCLUSIONS: This regimen can be carried out on outpatient basis and considerable response can be expected for pulmonary and pleural lesions.

Administration, Oral↗

PubMed2002

Survival associated with 5-fluorouracil-based adjuvant chemotherapy among elderly patients with node-positive colon cancer.

BACKGROUND: Randomized clinical trials have demonstrated the efficacy of adjuvant 5-fluorouracil (5-FU)-based chemotherapy after surgical resection of node-positive colon cancer. Although this treatment became the standard in 1990 following a National Institutes of Health Consensus Conference, among those at least 65 years of age it is less likely to be offered to older or nonwhite patients. OBJECTIVE: To determine the association between 5-fu-based chemotherapy and survival in older patients. DESIGN: Retrospective cohort study. SETTING: Combined database of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and Medicare. PATIENTS: 4768 patients 65 years of age or older who received a diagnosis of node-positive colon cancer from 1992 to 1996, were covered by Medicare Parts A and B, and resided in the population covered by the SEER program. MEASUREMENTS: Propensity scores to control for known predictors of receiving treatment, Cox proportional hazards models to assess the association of 5-FU therapy with survival, and sensitivity analyses to estimate the possible effects of unknown confounders. RESULTS: Fifty-two percent of patients received 5-FU therapy. For this sample, the hazard ratio for death associated with 5-FU therapy was 0.66 (95% CI, 0.60 to 0.73). Confounding could have accounted for this association only if an unmeasured confounder were extremely unequally distributed between the treated and untreated groups or increased mortality by at least 50%. CONCLUSIONS: 5-Fluorouracil adjuvant therapy is significantly associated with reduced mortality in older patients, similar to the association found in randomized, controlled trials among younger patients. More frequent use of 5-FU therapy in older patients would probably reduce death from colon cancer.

Age Factors↗

PubMed2006

[Thymidylate synthase gene promoter polymorphism in patients with advanced head and neck cancer treated by radio- and 5-fluorouracil chemotherapy].

AIM: Thymidylate synthase (TS) is a rate-limiting enzyme in the DNA synthetic pathway, and represents a cellular target of antimetabolite drug 5-fluorouracil. It catalyzes the reductive methylation of deoxyuridine-5'-monophosphate to deoxythymidine-5'-monophosphate. Inhibition of TS will result in depletion of both dTMP and, subsequently, dTTP. As a consequence, dUTP is misincorporated into DNA, resulting in DNA breakage and cell death. Developing resistance against 5-fluorouracil (FURA) based drugs might be due to the failure of inhibition of thymidylate synthase enzyme function. In the promoter region of the TS gene there is a tandem repeat sequence (2R or 3R), which was found to be polymorphic and influences the gene expression. Effectiveness and tolerability of Tegafur treatment might be influenced by expression of the TS gene. Our purpose was to determine the effectiveness and tolerability of concomitant radiotherapy and low-dose chemotherapy using Tegafur in respect of promoter polymorphism of thymidilate synthase gene. MATERIAL AND METHODS: TS promoter polymorphism (2R/2R, 2R/3R, 3R/3R) was determined by polymerase chain reaction using genomic DNA, in 47 patients with advanced head and neck cancer. RESULTS: Thirty patients out of 47 showed complete response, and genotyping of these patients revealed 2R/2R in 22 (73.3%), 2R/3R in 2 (6.7%) and 3R/3R in 6 (20%). Seventeen out of 47 patients reacted with partial response, and 2R/2R or 2R/3R were revealed in 5 (29.4%) and 3 (17.6%) patients, respectively, and 3R/3R genotype was identified in 9 patients (53%). CONCLUSION: We did not find any correlation between patient's data and response to therapy, but strong correlation was found between the latter and the patient's genotype. This facts indicate that the analysis of promoter polymorphism of thymidylate synthase gene might be a useful target to examine before FURA-based chemotherapy, and might allow to go into the direction of individualized treatment of head and neck cancer. We suppose that tumor response depends on genomic features of the patients.

Adult↗

PubMedDate not supplied

A phase II trial of etoposide, folinic acid, fluorouracil and epirubicin in advanced pancreatic carcinoma.

PURPOSE: Pancreatic carcinoma is generally considered a chemotherapy-resistant malignant neoplasm and to date there is no established chemotherapeutic treatment for patients with advanced disease. Many new combination regimens have been investigated to improve results. Modiano et al. (ASCO 1993; 12: 303) with ELF regimen (etoposide, folinic acid, and 5-fluorouracil) plus interferon obtained 6/7 partial remission in patients with advanced pancreatic cancer. Considering these interesting results and the therapeutic activity of epirubicin in this disease, we started a study (GOIM 9405) to verify the efficacy and safety of the ELFE (ELF + Epirubicin) regimen. PATIENTS AND METHODS: Twenty-three patients with advanced pancreatic cancer received etoposide 80 mg/m2 day 1-3, folinic acid (levo-isomer form) 100 mg/m2 day 1-3, 5-fluorouracil 340 mg/m2 day 1-3, and epirubicin 60 mg/m2 day 1. Treatment was repeated every three weeks. RESULTS: We obtained 3 PR, 4 SD and 13 PD. Overall response rate was 15% (95% CI: 3% to 38%) (intent to treat analysis: 13%; 95% CI: 3% to 34%). The median durations of response and survival were 9 and 5 months, respectively. Grade 3-4 WHO toxicity included diarrhoea (17%), mucositis (22%), leukopenia (17%). CONCLUSIONS: The ELFE regimen demonstrates scarce activity in patients with advanced pancreatic cancer, with mild toxicity.

Aged↗

PubMedDate not supplied

Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer: preliminary results of a Minnie Pearl Cancer Research Network phase II trial.

PURPOSE: To evaluate the feasibility, toxicity, and therapeutic efficacy of 1-hour paclitaxel, carboplatin, continuous low-dose infusional 5-fluorouracil, and concurrent radiation therapy administered preoperatively in patients with localized esophageal cancer. PATIENT AND METHODS: Forty-nine patients with localized esophageal cancer, of either squamous cell carcinoma or adenocarcinoma histology, were enrolled into this phase II trial. All patients were candidates for surgical resection and received the following neoadjuvant therapy: paclitaxel, 200 mg/m2, 1 hour IV on days 1 and 22; carboplatin, AUC 6.0, IV on days 1 and 22; 5-fluorouracil, 225 mg/m2/day, continuous IV infusion on days 1 to 42; and radiation therapy, 45 Gy, administered by 1.8-Gy daily fractions beginning on day 1 of chemotherapy. Upon completion of this neoadjuvant regimen, patients were reevaluated, and all responding patients were resected within 6 weeks of completing neoadjuvant treatment. RESULTS: Administration of this combined modality regimen was associated with moderate toxicity and was tolerated by most patients. Leukopenia (65%) and esophagitis (31%) were the most common toxicities. Most patients did not require nutritional support. There were no treatment-related deaths during neoadjuvant therapy; however, three patients (9%) experienced postoperative death. Preliminary assessment of treatment efficacy is encouraging, with 17 of 37 evaluable patients (46%) achieving pathologic complete remission and an additional 11 patients (30%) having only microscopic residual disease. CONCLUSIONS: This novel, combined-modality neoadjuvant approach for the treatment of localized esophageal carcinoma is feasible and can be administered with toxicity that compares favorably to previously reported neoadjuvant regimens containing high-dose cisplatin. Preliminary assessment of efficacy is also encouraging, with 46% of patients having pathologic complete response. Further follow-up and larger numbers of patients are required to assess efficacy more definitively.

Adenocarcinoma↗

PubMed1999

[The determination of individual sensitivity to 5-fluorouracil in patients with malignant tumors in different locations].

Possible determination of individual chemosensitivity of tumors to 5-fluorouracil was investigated using new original data and suggestions that lymphocytes of the tumor carrier have an ability to assimilate chemical drugs. Such an ability is likely due to the fact that 5-fluorouracil as an antimetabolite converted its action by inclusion of lymphocytes to the nucleic acid metabolism. The relation between the phenomenon and the chemotherapy efficacy is possibly realized through two mechanisms. One of them is the direct cytotoxic action of chemical drugs on lymphocyte tumor-associated clones resulting in impairment of the tumor growth control. The other is possible participation of lymphocytes in transport of chemical drugs to the tumor tissue. The in vitro model for estimation of tumor carrier chemosensitivity by the level of the nucleic acid metabolism reflects the impact of the immune system on realization of the antitumor effect of chemical drugs.

Antimetabolites, Antineoplastic↗