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PubMed1984

The effect of elimination of macrophages on the tissue distribution of liposomes containing [3H]methotrexate.

In the present study the tissue distribution of [3H]methotrexate was studied after intravenous injection of [3H]methotrexate-containing liposomes in normal and macrophage-depleted mice. Elimination of macrophages was performed by treatment with dichloromethylene diphosphonate- (DMDP)-containing liposomes. After thorough elimination of the macrophages from spleen and liver, by two intravenous injections of DMDP liposomes 6 and 4 days before tissue distribution studies, we found dramatic changes in the localization pattern of [3H]methotrexate liposomes in the blood, due to a decreased uptake of [3H]methotrexate liposomes by the DMDP liposome-treated liver. Because of the absence of these macrophages that are able to clear the blood of liposomes, and because of the resulting higher blood level of liposomes, we found an enhanced uptake of [3H]methotrexate liposomes by the spleen. It may be concluded that, in the spleen, apart from uptake of liposomes by macrophages, at least one other mechanism is responsible for the clearance of liposomes from the circulation. When comparing cholesterol-rich with cholesterol-poor liposomes, we found basically the same results, although uptake of cholesterol-rich liposomes by macrophages was smaller than that of cholesterol-poor liposomes, as found in several other studies. We suggest that pretreatment with DMDP liposomes can help to maintain a high level of intravenous-injected liposome-entrapped material in the blood, which otherwise would be removed by macrophages.

Animals↗

PubMed1992

Intramural methotrexate therapy for the prevention of neointimal thickening after balloon angioplasty.

OBJECTIVES: The study was performed to test the hypothesis that high local, intramural concentrations of antineoplastic agents at the site of balloon injury inhibit vascular smooth muscle cell proliferation without systemic toxicity. BACKGROUND: The predominant mechanism for recurrent stenosis after coronary balloon angioplasty is neointimal thickening due to medial smooth muscle cell proliferation. The clinical use of potent antiproliferative agents to prevent restenosis has been limited by the potential for severe systemic side effects. Local therapy with these agents may be effective and free of systemic complications. METHODS: After bilateral balloon angioplasty of the carotid arteries of 14 juvenile farm pigs, the dilated arterial segments were treated locally with methotrexate (6.25 mg/ml, total dose 25 mg) or 0.9% saline solution through a perforated balloon catheter. The animals were then killed 30 days after balloon injury to determine the effects of this therapy on neointimal thickness. In an additional six animals, tritium-labeled methotrexate was used to determine the concentration and duration of detectability of methotrexate in the wall of the treated arteries and in the systemic circulation. RESULTS: Two hours after drug instillation the concentration of labeled drug was greater than 1,000-fold greater in the wall of the treated artery than in circulating blood, and this ratio remained between 50 and 100 for at least 7 days. Despite this difference, the mean intimal thickness 30 days after the procedure was similar in the 10 methotrexate-treated arteries and the 18 saline-treated arteries (59 +/- 30 vs. 56 +/- 25 microns, p = 0.6). The morphologic appearance of the neointima was similar in each group and suggested an important role for mural thrombus in the genesis of the intimal thickening. CONCLUSIONS: Treatment with intramural methotrexate, delivered through a perforated balloon catheter at the selected concentration and total dose, failed to prevent intimal thickening after balloon injury. Nonetheless, the perforated balloon catheter appears to be a promising means of delivering a high local concentration of drugs with potentially life-threatening systemic side effects. The optimal concentrations and combinations of candidate drug therapies warrant further evaluation.

Angioplasty, Balloon↗

PubMed1992

Potentiation of etoposide cytotoxicity against a human ovarian cancer cell line by pretreatment with non-toxic concentrations of methotrexate or aphidicolin.

Exposure of human ovarian cancer SW626 cell line to 0.08 mumol/l methotrexate or 25 mumol/l aphidicolin for 24 h caused no cytotoxicity but enhanced etoposide cytotoxicity. Methotrexate or aphidicolin treatment induced a reversible blockade at the beginning of S phase which was reversed upon drug removal with a consequent wave of synchronisation. The enhancement of etoposide cytotoxicity was not due to higher etoposide intracellular uptake in the methotrexate or aphidicolin-pretreated cells. The topoisomerase II content in methotrexate or aphidicolin pretreated SW626 cells was higher than in control cells assessed by western blotting or flow cytometry. The higher etoposide cytotoxicity observed after synchronization with methotrexate or aphidicolin was apparently unrelated to the number of drug-induced DNA-topoisomerase II complexes evaluated as DNA double strand breaks or DNA-protein crosslinks. These data support the view that etoposide-induced DNA-topoisomerase II complexes are more cytotoxic in cells which are in S-phase.

Aphidicolin↗

PubMed1992

Assay for expression of methotrexate-resistant dihydrofolate reductase activity in the presence of drug-sensitive enzyme.

A simple, continuous spectrophotometric assay for dihydrofolate reductase (DHFR) activity was adapted for determination of drug-resistant enzyme activity expressed from transfected genes in cells containing drug-sensitive enzyme. Methotrexate inhibition characteristics in this assay system were assessed for the murine wild-type (WT) enzyme as well as variant genes encoding amino acid substitutions at codon positions 22 (arg22) or 31 (trp31) expressed in DHFR-deficient Chinese hamster ovary (CHO) cells and in mouse 3T3 cells. Methotrexate concentrations were thus identified which maximized inhibition of the wild-type enzyme while maintaining substantial arg22 or trp31 activity. Mixing experiments were conducted to determine the minimum amount of drug-resistant enzyme distinguishable from a constant amount of wild-type enzyme in the presence of methotrexate. Mixtures of enzymes from a variety of sources (WT, arg22, or trp31 expressed in CHO or 3T3 cells) demonstrated a detection limit of 0.03 to 0.06 nmol/min. Assay of methotrexate-resistant arg22 DHFR appeared to be limited by the low level of activity associated with this enzyme variant, whereas assay of the trp31 variant was limited by enzyme inhibition at lower concentrations of methotrexate. The assay was thus applicable to two quite diverse DHFR variants and may be useful for assaying the expression of other drug-resistant DHFR genes as well after introduction into cells containing drug-sensitive enzyme.

3T3 Cells↗

PubMed2006

Single-dose methotrexate regimen in the treatment of low-risk gestational trophoblastic neoplasia.

OBJECTIVE: The objective of the study was to evaluate the effectiveness of single-dose methotrexate in women with low-risk gestational trophoblastic neoplasia. STUDY DESIGN: In this prospective observational cohort study, 105 women with low-risk gestational trophoblastic neoplasia were treated with an intravenous bolus of 100 mg/m2 of methotrexate followed by a 12-hour infusion of 200 mg/m2. If the human chorionic gonadotropin level fell 10-fold after 2 weeks, no further chemotherapy was given. Characteristics between the 2 groups with or without complete remission with this regimen were compared. RESULTS: The overall complete remission rate with methotrexate was 84.8%, with 44.8% of women requiring a single dose of methotrexate alone. The pretreatment human chorionic gonadotropin level was found to be significantly higher in women who failed the single-dose methotrexate regimen (P = .001), and 10 of 11 patients with metastases required further doses. CONCLUSION: This regimen offers an effective option for women with low-risk gestational trophoblastic neoplasia without metastases and a low pretreatment human chorionic gonadotropin level.

Adolescent↗

PubMed2006

Use of "2-dose" regimen of methotrexate to treat ectopic pregnancy.

OBJECTIVE: To evaluate the safety and acceptability of a novel dosing regimen of methotrexate to treat ectopic pregnancy. DESIGN: Prospective study. SETTING: Three academic medical centers. PATIENT(S): One hundred one patients with ectopic pregnancy who elected to have medical therapy. INTERVENTION(S): Intramuscular methotrexate 50 mg/m(2) was administered on days 0 and 4; additional doses of methotrexate were given on day 7 and/or day 11 if hCG levels did not decrease by 15% during the follow-up period. MAIN OUTCOME MEASURE(S): Adverse events, acceptability, and resolution of pregnancy without surgical treatment. RESULT(S): With this protocol, 87% of patients were treated successfully. Of those protocols that were considered failures, only 3% of patients experienced rupture of ectopic pregnancy. Treatment was well-tolerated; most side effects were reported as mild and transient. Ninety-one percent of the 61.5% of patients who responded to the satisfaction questionnaire reported satisfaction with this regimen. CONCLUSION(S): This "2-dose" protocol minimizes the number of injections and surveillance visits, compared with the "multiple dose" regimen, and methotrexate is administered more frequently than with the "single dose" regimen. The protocol may optimize the balance between convenience and efficacy. In a limited number of women, no safety concerns were noted with up to 4 doses of methotrexate in a 2-week period without leucovorin rescue.

Adult↗

PubMed2006

Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: a systematic review.

OBJECTIVE: Successful medical management of an ectopic pregnancy is inversely associated with initial hCG level. The purpose of this publication is to assess whether there is a level of hCG above which failure rate substantially increases. DESIGN: A systematic review and summary analysis was performed, including studies reporting methotrexate treatment outcomes as stratified by various hCG ranges. SETTING: Academic medical center. PATIENT(S): Review of published information regarding patients treated with methotrexate. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Success and failure rate of medical management. RESULT(S): Five observational studies, including 503 women, were found that reported successes in using single-dose methotrexate stratified by initial hCG concentration. Failure rates increase with increasing hCG levels. A substantial and statistically significant increase in failure rates is seen when comparing patients who have initial hCG levels of >5,000 mIU/mL with those who have initial levels of <5,000 mIU/mL (odds ratio: 5.45; 95% confidence interval: 3.04, 9.78). The failure rate for women who had an initial concentration between 5,000 and 9,999 mIU/mL was significantly higher than that for those who had initial levels between 2,000 and 4,999 mIU/mL (odds ratio: 3.76; 95% confidence interval: 1.16, 12.33). CONCLUSION(S): Results support a substantial increase in failure of medical management with single-dose methotrexate when the initial hCG is above 5,000 mIU/mL. Methotrexate should be used with caution in patients with ectopic pregnancy who present with hCG levels above this level.

Chorionic Gonadotropin↗

PubMed2005

Autoantibody induction in patients with refractory spondyloarthropathy treated with infliximab and methotrexate.

OBJECTIVES: Induction of antinuclear antibodies (ANA) has been reported in patients taking infliximab to treat refractory spondyloarthropathy, without concomitant methotrexate therapy. We investigated antibody induction in patients with spondyloarthropathy treated with both infliximab and methotrexate. METHODS: In 33 patients meeting ESSG criteria for spondyloarthropathy, infliximab was given (infusions at weeks 0, 2, 6, 14, 22, and 30) in combination with methotrexate (10-25 mg/week). At baseline, 6 and 30 weeks after treatment initiation, the patients underwent indirect immunofluorescence testing for ANA and ELISAs for antibodies to double-stranded DNA, soluble nuclear antigens, and histones. RESULTS: As compared to baseline, significant increases were found at week 30 in the number of patients with ANA (4% vs. 29%, P = 0.02), IgG antihistone antibodies (7% vs. 29%, P = 0.04), and IgM antihistone antibodies (29% vs. 57%, P = 0.03). No significant increases were noted for antibodies to double-stranded DNA or to soluble nuclear antigens. No cases of clinical lupus syndrome were recorded. CONCLUSION: Autoantibody induction was far less common in our patients than in the population studied by De Rycke et al. [Arthritis Rheum. 48 (2003) 1015], who found ANA in 88.6% and antibodies to double-stranded DNA in 17.1% of 35 patients taking infliximab without methotrexate. Methotrexate may reduce the risk of autoantibody induction and disimmunity associated with infliximab therapy.

Adult↗

PubMed2026

Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial.

OBJECTIVE: Stratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP. DESIGN: Plasma/serum samples from participants in PROMOTE's biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj). RESULTS: 87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-α levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-months. Analysing within this active treatment randomised arm, higher baseline IFN-γ was associated with greater reduction in NRS pain change (0.66 [0.01, 1.31], P=0.047), as was decreasing TNF-α over 6-months (2.25 [0.00, 4.5], P=0.049). LASSO identified higher IFN-γ, lower plasma IL-15 and IL-16, and younger age as the most important baseline predictors of pain improvement. hs-CRP was highly selected by LASSO for treatment response in both arms. In a secondary univariate treatment arm-by-biomarker interaction analysis, of the 19 markers, only hs-CRP showed consistent effects in adjusted models (at baseline, coeffic. 2.34 [0.53, 4.15], P=0.001; change over 6-months, (0.36 [0.06, 0.66], P=0.018). CONCLUSIONS: Blood measurement of IFN-γ, TNF-α, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.

Humans↗

PubMed1985

Methotrexate with citrovorum factor rescue in gestational trophoblastic disease.

Thirty-three patients with gestational trophoblastic disease treated with methotrexate alone and 68 similar patients treated with methotrexate and citrovorum factor rescue were analyzed. Both groups showed a comparable sustained biochemical remission rate. The group treated with methotrexate and citrovorum factor however showed a shorter interval to induction of remission (p less than 0.05). Contrary to previous reports, the methotrexate and citrovorum factor regimen failed to protect the patients against the development of hepatic toxicity, the incidence of hepatic toxicity being significantly higher in the group treated with methotrexate and citrovorum factor.

Adult↗

PubMed1997

Abortion induced with methotrexate and misoprostol: a comparison of various protocols.

Seven hundred fifty-six women had abortions induced with methotrexate and misoprostol. Various protocols were compared. In Group 1, phase 1, after receiving 50 mg/m2 methotrexate IM, 289 women were randomized to receive either 750 or 500 micrograms of vaginal misoprostol. In Group 1, phase 2, 84 women who had failed to abort after one dose of misoprostol were randomized to receive either vaginal or oral routes for the second dose of misoprostol given on Day 8. In Group 2, a cohort of 226 women who received 60 mg/m2 methotrexate were compared to the 289 women who received 50 mg/m2 in Group 1. There were no differences in rates of effectiveness in the various trial groups. Side effects were greater with 60 mg/m2 of methotrexate. In Group 3, a cohort of 241 women received the misoprostol in three vaginal doses 8 hr apart starting on Day 5, and were compared to the 289 women in Group 1 receiving one vaginal dose. In women whose medical abortion failed, fetuses were found to have limb abnormalities In the total group of 756 women, 88.8% aborted successfully without surgical aspiration, with only minor side effects, and the acceptance rate was high. This study indicates that medical abortions induced with methotrexate and misoprostol are safe and effective, but more research is needed to find a more effective protocol.

Abortifacient Agents, Nonsteroidal↗

PubMed1997

Misoprostol 3, 4, or 5 days after methotrexate for early abortion. A randomized trial.

A randomized trial was conducted including 287 pregnant women seeking elective abortion to compare the efficacy of misoprostol given 3, 4, or 5 days after methotrexate for abortion at < or = 63 days' gestation. Subjects received 50 mg/m2 methotrexate intramuscularly and were randomly allocated to self-administer vaginally 800 micrograms of misoprostol 3, 4, or 5 days after the methotrexate. The misoprostol dose was repeated 48 and 96 h later if the abortion did not occur. Outcome measures included successful abortion (complete abortion without requiring a surgical procedure), and side effects. Eighty-six cases (93%; 95% confidence interval [CI] 85%-97%) aborted in Group I; 90 cases (92%; 95% CI 84%-96%) aborted in Group II (relative risk [RR] = 1.09; RR 95% CI 0.38-3.14); and 89 (93%; 95% CI 86%-97%) cases aborted in Group III (RR = 0.97; RR 95% CI 0.33-2.87). No significant statistical differences were obtained for the success rates when misoprostol was given days 3, 4, or 5 after the administration of methotrexate (p = 0.97) nor with any of the characteristics of the subjects. Complete abortion occurred in 265/287 (92%; 95% CI 89%-95%) patients. Twenty-two cases (8%; 95% CI 5%-11%) resulted in failure. Side effects for methotrexate were minimal while for misoprostol they were moderate. This combination could be an alternative to surgical abortion or the use of antiprogestins and prostaglandins for medical abortion.

Abortifacient Agents, Nonsteroidal↗

PubMed1999

Methotrexate produces delayed emesis in dogs: a potential model of delayed emesis induced by chemotherapy.

We investigated the emetic effects of cisplatin and methotrexate in dogs, the effects of ondansetron on cisplatin-induced vomiting, and the effects of ondansetron, dexamethasone and a combination of the two on the vomiting induced by methotrexate. Ondansetron was administered 30 min before cisplatin administration. Ondansetron, dexamethasone or a combination of the two was administered 8, 24 and 48 h after methotrexate administration. Cisplatin (3 mg/kg, i.v.) induced acute vomiting but failed to induce delayed vomiting. The acute vomiting was markedly inhibited by ondansetron (3 mg/kg, p.o.; 1 mg/kg, i.v.). Methotrexate (2.5 mg/kg, i.v.) caused delayed vomiting, which was partly inhibited by ondansetron (1 mg/kg, i.v.) or dexamethasone (2.5 mg/kg, i.v.). The combination of the two agents was more effective. These results suggest that methotrexate-induced emesis in dogs would be useful for studying delayed emesis.

Animals↗

PubMed2000

Predictors of treatment failure for ectopic pregnancy treated with single-dose methotrexate.

OBJECTIVE: To determine variables that predict treatment failure after methotrexate (MTX) treatment of ectopic pregnancy. DESIGN: Retrospective cohort study. SETTING: Canadian teaching hospital. PATIENT(S): Sixty patients diagnosed with and treated for ectopic pregnancy. INTERVENTION(S): A single dose of methotrexate (50 mg/m(2)) by i.m. injection. MAIN OUTCOME MEASURE(S): Resolution of serum beta-hCG or clinical evidence of treatment failure. RESULT(S): Treatment failure was observed following methotrexate administration in 65% of cases when initial beta-hCG was >4000 IU/L, but in only 7. 5% of patients when serum beta-hCG was <4000 IU/L (OR = 52.06, 95% CI 4.88-555.56). Patients who presented with pelvic pain without tenderness had treatment failure 56% of the time versus only 17% in those without pain (OR = 9.20, 95% CI 1.02-82.60). Treatment failure also occurred in 53% of patients presenting with vaginal bleeding versus 16% without bleeding (OR = 6.18, 95% CI 0.73-51.93). CONCLUSION(S): Methotrexate should not be used to treat ectopic pregnancy when initial beta-hCG is >4000 IU/L. Caution should also be exercised in using methotrexate for ectopic pregnancy when the patient presents with bleeding or pain even without tenderness.

Abortifacient Agents, Nonsteroidal↗

PubMed2002

Efficacy of methotrexate treatment in extrauterine pregnancies defined by stable or increasing human chorionic gonadotropin concentrations.

OBJECTIVE: To evaluate the efficacy of methotrexate treatment in selected cases of extrauterine pregnancy (EUP) defined by stable or increasing hCG concentration. DESIGN: Prospective cohort study. SETTING: Gynecology department of the Lis Maternity Hospital. PATIENT(S): Fifty women with EUP diagnosed whenever an intrauterine gestational sac was not seen on transvaginal ultrasonography. INTERVENTION(S): Women received IM methotrexate at a dose of 50 mg/m(2) of body surface area. Failure of hCG levels to fall by >/=15% during any successive week resulted in repeated administration of methotrexate. Surgical intervention was performed for presumed tubal rupture. MAIN OUTCOME MEASURE(S): Serial hCG measurement was performed weekly until hCG concentration reached 15 mIU/mL. Success was defined as the achievement of hCG concentration of 25 mIU/mL without surgical intervention. RESULT(S): Forty-four women (88%) were successfully treated. The mean time from first methotrexate injection to success was 34 +/- 2.4 days. Women treated successfully and unsuccessfully differed significantly only with regard to serum hCG levels of 1,876 +/- 243 and 3,489 +/- 376 mIU/mL, respectively. When the initial hCG levels were lower or higher than 2,000 IU/L, the success rate was 97% and 74%, respectively (significant by Fisher's exact test). CONCLUSION(S): When methotrexate treatment is administrated in a selected group of EUP defined by stable or increasing hCG, it may fail more frequently (26%) when initial hCG levels are >2,000 mIU/mL.

Chorionic Gonadotropin↗

PubMed1998

Systemic methotrexate therapy versus laparoscopic salpingostomy in patients with tubal pregnancy. Part I. Impact on patients' health-related quality of life.

OBJECTIVE: To compare patients' health-related quality of life after systemic methotrexate therapy versus laparoscopic salpingostomy for tubal pregnancy. DESIGN: Multicenter randomized clinical trial. SETTING: Departments of obstetrics and gynecology of six Dutch hospitals. PATIENT(S): Hemodynamically stable patients with a laparoscopically confirmed unruptured tubal pregnancy without signs of active bleeding, who were randomly assigned to undergo either systemic methotrexate therapy or laparoscopic salpingostomy. INTERVENTION(S): Standard health-related quality of life questionnaires administered before and 2 days, 2 weeks, 4 weeks. and 16 weeks after confirmative laparoscopy. MAIN OUTCOME MEASURE(S): Health-related quality of life. RESULT(S): Health-related quality of life was impaired most severely 2 days after confirmative laparoscopy in both treatment groups and improved during follow-up. Health-related quality of life was impaired more severely after systemic methotrexate therapy than after laparoscopic salpingostomy. Medically treated patients had more limitations in physical functioning, role functioning, and social functioning; had worse health perceptions, less energy, more pain, more physical symptoms, and a worse overall quality of life; and were more depressed than surgically treated patients. CONCLUSION(S): Systemic methotrexate therapy had a more negative impact on patients' health-related quality of life than did laparoscopic salpingostomy. This negative impact on patients' health-related quality of life of systemic methotrexate therapy should be taken into account when deciding on the appropriate therapy for tubal pregnancy.

Adaptation, Psychological↗

PubMed1999

Single high dose of local methotrexate for the management of relatively advanced ectopic pregnancies.

OBJECTIVE: To evaluate the limits of the conservative management of relatively advanced ectopic pregnancies (EPs) with local methotrexate given at a higher than standard dose. DESIGN: Nonrandomized prospective study. SETTING: A tertiary teaching hospital and an affiliated infertility center. PATIENT(S): We treated 118 EPs of up to 56 days' gestation (8 weeks) regardless of the presence of fetal heart activity, the size of the gestational mass, and the initial beta-hCG levels. INTERVENTION(S): Transvaginal intraamniotic or laparoscopic intratubal injection of 100 mg of methotrexate as a single dose. MAIN OUTCOME MEASURE(S): beta-hCG levels, red and white blood cell count, and liver function tests before and after methotrexate injection, followed by repeat transvaginal color Doppler assessments. RESULT(S): Treatment was successful in 105 (88.98%) of the 118 patients included in the study. In 7 of them with persistent fetal cardiac activity after the methotrexate injection, treatment was concluded with a complementary intracardiac injection of 10% KCl. No grade 3 or important clinical, hematologic, or biochemical toxicities occurred. CONCLUSION(S): Local administration of a single high dose of methotrexate (100 mg) proved safe and effective in the medical management of relatively advanced and unselected EPs, including cases with fetal heart activity, with high initial beta-hCG levels, and with a gestational mass beyond the standard maximum of 3.5 cm. Complementary hypertonic KCl proved to be effective in cases with persistent cardiac activity.

Adult↗

PubMed1985

The fate of the bladder in patients with metastatic bladder cancer treated with cisplatin, methotrexate and vinblastine: a Northern California Oncology Group study.

We report the efficacy and toxicity of combined cisplatin, methotrexate and vinblastine for the treatment of metastatic transitional cell carcinoma of the bladder in 50 evaluable patients. Of these 50 patients 17 had not undergone cystectomy and had residual invasive bladder cancer. Of these 17 patients 11 had complete response of the bladder lesions following cisplatin, methotrexate and vinblastine for metastatic disease, including 6 of 12 treated by cisplatin, methotrexate and vinblastine alone, and 5 of 5 treated with cisplatin, methotrexate and vinblastine plus palliative or preoperative pelvic irradiation. Complete response was confirmed in 10 of the 11 patients by endoscopy and biopsy, and in 1 by cystectomy. One patient whose liver metastasis responded to cisplatin, methotrexate and vinblastine had conversion to complete response by cystectomy for persistent bladder cancer. Of these 17 patients 7 are alive, including 5 without disease, 4 to 41 months after treatment. The bladder appears to be responsive to this combination chemotherapy for invasive transitional cell carcinoma. This experience underscores the need for regular pathological re-staging of the bladder cancer in patients receiving chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗