levoleucovorin and Ovarian-Neoplasms

Topics: Adenocarcinoma, Mucinous; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colonic Neoplasms; Combined Modality Therapy; Diagnosis, Differential; Female; Fluorouracil; Gallbladder; Genes, ras; Humans; Hyperthermia, Induced; Intestines; Leucovorin; Middle Aged; Neoadjuvant Therapy; Omentum; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Remission Induction; Round Ligaments; Second-Look Surgery

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carboplatin; Combined Modality Therapy; Cystadenofibroma; Diagnosis, Differential; Female; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Parenteral; Irinotecan; Leucovorin; Mesothelioma; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Organoplatinum Compounds; Ovarian Neoplasms; Ovariectomy; Oxaliplatin; Paclitaxel; Pemetrexed; Peritoneal Neoplasms

Oxaliplatin is a platinum compound that inhibits DNA synthesis, primarily by causing intrastrand cross-links in DNA. Oxaliplatin has a broad spectrum of antineoplastic activity and has demonstrated a lack of cross-resistance with other platinum compounds. In patients with metastatic colorectal cancer, intravenous oxaliplatin has been trialled as a monotherapy and in combination with other agents. The highest response rates were achieved when oxaliplatin was used in combination with fluorouracil/folinic acid (leucovorin; calcium folinate), typically > or = 50% in the first-line setting and 13 to 45% as a second-line therapy. First-line triple therapy with oxaliplatin and fuorouracil/folinic acid achieved significantly higher response rates and longer median progression-free survival than fluorouracil/folinic acid therapy alone. However, no significant difference in the median duration of overall survival was found. This may be a consequence of the subsequent use of oxaliplatin and/or surgery after disease progression in patients who relapsed after fluorouracil/folinic acid therapy alone. Neoadjuvant therapy with oxaliplatin/fluorouracil/folinic acid has proven beneficial in enabling surgical removal of previously unresectable liver metastases. In 2 studies, surgery with curative intent was performed in 16 and 51% of patients with initially unresectable liver metastases following oxaliplatin/fluorouracil/folinic acid therapy; the 5-year survival rates were 40 and 50%, respectively. In patients with advanced ovarian cancer, first-line therapy with oxaliplatin/cyclophosphamide achieved an objective response rate which did not differ significantly from that of cisplatin/cyclophosphamide (33 vs 42%). In addition, oxaliplatin has shown efficacy in patients with platinum-pretreated ovarian cancer and achieved objective response rates similar to paclitaxel in this setting (16 vs 17%). Promising results have also been found with oxaliplatin in patients with non-Hodgkin's lymphoma, breast cancer, mesothelioma and non-small cell lung cancer. Reversible, cumulative, peripheral sensory neuropathy is the principle dose-limiting factor of oxaliplatin therapy. Haematological and gastrointestinal toxicities occur frequently but are generally mild to moderate in intensity.. Oxaliplatin in combination with fluorouracil/folinic acid is an effective treatment option for patients with metastatic colorectal cancer, both as a first-line therapy and in patients refractory to previous chemotherapy. Although preliminary results failed to show any overall survival advantage of this regimen over fluorouracil/folinic acid alone, this may be a consequence of trial design and requires further examination. Additional clinical investigation of oxaliplatin in patients with other cancers is warranted given the promising results achieved in early trials, most notably in patients with platinum-pretreated ovarian cancer.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biotransformation; Clinical Trials as Topic; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Metabolic Clearance Rate; Organoplatinum Compounds; Ovarian Neoplasms; Oxaliplatin; Tumor Cells, Cultured

Topics: Antineoplastic Combined Chemotherapy Protocols; Biological Transport; Biotransformation; Cell Line; Colorectal Neoplasms; Female; Fluorouracil; Folic Acid; Humans; Leucovorin; Ovarian Neoplasms; Tetrahydrofolates; Tumor Cells, Cultured

Recent clinical studies on patients with malignancies, who were treated with UHF and LMWHs raised the possibility, that these agents may possess an inhibitory effect on tumor progression. Further studies supported that this effect is independent from the anticoagulant and antithrombotic action. In this retrospective study oncological patients with an increased risk for thromboembolism were choosen, who received prophylactic treatment with an LMWH (nadroparin) at least for 6 months. Comparing with the control group, in some subgroups (T3 and T4, as well as M1) the LMWH-treated patients showed a significantly increased survival.

Topics: Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Colonic Neoplasms; Cyclophosphamide; Disease Progression; Epirubicin; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Nadroparin; Neoplasm Staging; Ovarian Neoplasms; Paclitaxel; Pilot Projects; Retrospective Studies; Survival Analysis; Time Factors

The prognosis of patients with platinum refractory disease is dismal. We present data from heavily pretreated patients to whom the folinic acid, 5-fluorouracil and oxaliplatin (Folfox) regimen was administered. The objectives were to assess response rate and to evaluate the safety profile.. Patients with recurrent, resistant or refractory pretreated ovarian carcinoma were eligible for oxaliplatin (85 mg/m(2)) and leucovorin (200 mg/m(2)), both given as a 2-h infusion on day 1, followed by a 48-h infusion of 5FU 2,600 mg/m(2) every 2 weeks.. Fourteen patients were treated. Median age: 56 years (49-70). Median number of previous chemotherapy regimens: 5 (3-10) and previous platinum-based regimens: 2 (1-3). Median chemotherapy-free interval (interval since the completion of the last-line chemotherapy before the administration of the Folfox regimen): 9.5 weeks (1-39). Median number of administered cycles of Folfox/patient: 8 (2-11 cycles). Two (14.5%) patients had a disease complete response, 2 (14.5%)-partial response, 4 (29%)-stable disease and 6 (43%)-progressive disease. Four (29%) patients had a CA-125 complete response, 2 (14.5%)-CA-125 partial response, 5 (35.5%)-stable CA-125 levels and 3 (21%)-progressive CA-125 levels. There were no grade 4 adverse events or deaths due to the treatment. No dose modifications were required due to toxicity.. Folfox seems to be a valuable option for heavily pre-treated patients with ovarian cancer, with an overall response rate, according to RECIST criteria, of 29% and disease stabilization in an additional 29% of patients, with a manageable toxicity profile. These results support further assessment of Folfox as salvage treatment for patients with carcinoma of the ovary or fallopian tube.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cohort Studies; Disease-Free Survival; Fallopian Tube Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Ovarian Neoplasms; Oxaliplatin; Treatment Outcome

To evaluate the efficacy and toxicity of Oxaliplatin and 5-Fluorouracil (5-FU)/Leucovorin (LV) combination in ovarian cancer relapsing within 2 years of prior platinum-based chemotherapy in a phase II trial.. Eligible patients had at least one prior platinum-based chemotherapy regimen, elevated CA-125 > or = 60 IU/l, radiological evidence of disease progression and adequate hepatic, renal and bone marrow function. Patients with raised CA-125 levels alone as marker of disease relapse were not eligible. Oxaliplatin (85 mg/m(2)) was given on day 1, and 5-Fluorouracil (370 mg/m(2)) and Leucovorin (30 mg) was given on days 1 and 8 of a 14-day cycle.. Twenty-seven patients were enrolled. The median age was 57 years (range 42-74 years). The median platinum-free interval (PFI) was 5 months (range 0-17 months) with only 30% of patients being platinum sensitive (PFI > 6 months). Six patients (22%) had two prior regimens of chemotherapy. A total of 191 cycles were administered (median 7; range 2-12). All patients were evaluable for toxicity. The following grade 3/4 toxicities were noted: anemia 4%; neutropenia 15%; thrombocytopenia 11%; neurotoxicity 8%; lethargy 4%; diarrhea 4%; hypokalemia 11%; hypomagnesemia 11%. Among 27 enrolled patients, 20 patients were evaluable for response by WHO criteria and 25 patients were evaluable by Rustin's CA-125 criteria. The overall response rate (RR) by WHO criteria was 30% (95% CI: 15- 52) [three complete responses (CRs) and three partial responses (PRs)]. The CA-125 response rate was 56% (95% CI: 37-73). Significantly, a 25% (95% CI: 9-53) radiological and a 50% (95% CI: 28-72) CA-125 response rate were noted in platinum resistant patients (PFI < 6 months). The median response duration was 4 months (range 3-12) and the median overall survival was 10 months.. Oxaliplatin and 5-Fluorouracil/Leucovorin combination has a good safety profile and is active in platinum-pretreated advanced epithelial ovarian cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; CA-125 Antigen; Disease Progression; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Oxaliplatin

A prospective phase II study was conducted to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluoruracil (5-FU) and high-dose leucovorin (LV) (FOLFOX-4) in patients with platinum-resistant, taxane-pretreated recurrent ovarian cancer.. Thirty-eight patients, with a median age of 58 years (range 33-77), were treated with oxaliplatin 85 mg m(-2) as a 2-h infusion on day 1, LV 200 mg m(-2) day(-1) as a 2-h infusion followed by bolus 5-FU 400 mg m(-2) day(-1) and a 22-h infusion of 5-FU 600 mg m(-2) day(-1) for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles.. The vast majority of patients had performance status 0 or 1 and 76.3% had > or = 2 metastatic sites. A median number of four cycles per patient (range, 1-8) were administered. Based on an intention-to-treat analysis, 3 patients (7.9%) achieved a complete response (CR) and 8 (21.1%) achieved a partial response (PR), for an overall response rate of 29%. Another 29% of patients had stable disease (SD). The median relapse-free survival was 5.2 months (range 2.5-17), the median time to tumor progression was 4.8 months (range 0.6-19), and the median overall survival was 10.1 months (range 0.2-36). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 29% and 21.1% of patients, respectively. Febrile neutropenia was encountered in 3 patients (7.9%), who were successfully treated. Grade 3/4 neurotoxicity developed in 15.8% of patients; neurotoxicity gradually declined after treatment discontinuation. Alopecia, nausea-vomiting, diarrhea, mucositis, and asthenia were not a serious problem. There were no treatment-related deaths.. The combination of oxaliplatin and 5-FU/LV (FOLFOX-4) appears to be an effective regimen with a good toxicity profile for the treatment of platinum-resistant, taxane-pretreated ovarian cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Oxaliplatin; Paclitaxel; Prospective Studies; Salvage Therapy

In this Phase I study, the maximally tolerated doses (MTDs) of i.p. iododeoxyuridine (IdUrd) alone and in combination with i.v. calcium leucovorin (LV) were determined. The pharmacokinetics and pharmacological advantage of IdUrd were evaluated, and flow cytometric analysis allowed examination of the extent of incorporation of IdUrd into tumor cells with and without the addition of i.v. LV. Thirty-nine patients with advanced neoplasms primarily confined to the peritoneal space were enrolled in a dose-escalation trial using 4-h dwells of IdUrd administered i.p. daily for 4 days with and without an i.v. infusion of LV 500 mg/m2/day for 4.5 days. Twenty-three patients received single-agent therapy, and 13 patients received i.p. IdUrd in combination with i.v. LV. The MTD of single-agent IdUrd administered on this schedule was 4125 mg/m2/day for 4 days; and that of the IdUrd in combination was 3438 mg/m2/day. Dose-limiting toxicities were myelosuppression and stomatitis. During the period of the dwell, the peritoneal AUC (area under the curve) of IdUrd exceeded the plasma AUC of IdUrd by one or two orders of magnitude in all patients at all doses tested; there was a possible effect of LV on peritoneal AUC. The geometric mean pharmacological advantage (AUCperitoneal/ AUCplasma) was 181 at 625 mg/m2/day and 90 at 4538 mg/m2/day. Flow cytometric analysis suggests saturation of IdUrd measured in DNA at the 2500-3125 mg/m2 dose level, without an increase after the addition of LV. Twelve patients received 4-12 courses of therapy. One patient with recurrent ovarian cancer who received 16 courses of therapy experienced complete resolution of her ascites, near normalization of CA-125 levels, and improved quality of life; two patients with high-risk tumors receiving "adjuvant" therapy are disease-free at 3 and 6 years after treatment; other patients experienced transient clearing of ascites. The recommended Phase II dose of i.p. IdUrd using a 4-h dwell daily for 4 days is 3750 mg/m2/day alone or 3125 mg/m2/day in combination with continuous i.v. LV at 500 mg/m2/day for 4.5 days. Although flow cytometric data suggest that DNA incorporation of IdUrd is not affected by the addition of LV, the cytotoxicity of the combination regimen may be increased due to LV-enhanced, IdUrd-related inhibition of thymidylate synthase. For this reason, we recommend that efficacy studies of the combination continue in parallel with studies of IdUrd alone.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; CA-125 Antigen; DNA, Neoplasm; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastrointestinal Neoplasms; Humans; Idoxuridine; Injections, Intraperitoneal; Injections, Intravenous; Leucovorin; Male; Middle Aged; Ovarian Neoplasms; Pancreatic Neoplasms; Peritoneal Neoplasms

A total of 14 patients with platinum-resistant advanced epithelial ovarian cancer were treated with a continuous infusion of high-dose 5-fluorouracil (5-FU, 1200 mg/m2 per day) for 2 consecutive days weekly for 4 weeks and, thereafter, every 2 weeks in combination with a push injection of folinic acid (20 mg/m2) given just before 5-FU and after 24 h. No objective response was documented, and only five patients showed stable disease. The median survival was 6.5 months. There was minimal toxicity. This schedule of 5-FU in combination with folinic acid is not effective as second-line chemotherapy in advanced ovarian cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Cisplatin; Drug Resistance; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Ovarian Neoplasms; Survival Rate

Cisplatin (CDDP) administration by the intra-arterial hepatic route (i.a.h.) in patients with primary or metastatic liver malignancies could enhance the anti-tumor activity of the drug and reduce its systemic toxicity. The aim of the present study was to compare Pt pharmacokinetics and the toxicity of the circulating drug after i.a.h. versus intravenous (i.v.) administration. CDDP pharmacokinetics was followed-up in 11 i.a.h. courses given to 7 patients with liver malignancies and compared with 19 i.v. courses in 15 patients with cancer of different origins. The Pt level in blood was monitored by sensitive atomic absorption spectrometry. The dose given was in the range of 25-80 mg/m2/treatment. For analysis and for comparison purposes, the data from both CDDP treatments were normalized to a standard dose of 35 mg/m2. The mean peak Pt level for i.a.h. treatment was found to be about half of the mean peak value for i.v. administration with a similar dose-independent bi-exponential rate of elimination i.a.h. CDDP treatment was relatively well tolerated with no symptoms of either nephro- or neurotoxicity. For in vitro evaluation of peripheral CDDP toxicity, a sensitive ovarian carcinoma cell line, OV-1063, was used. A cytotoxic effect was recorded only within 2 hr following high-dose i.v. CDDP treatment. A substantial fraction of the drug given by the i.a.h. route was found to be extracted by the liver in the first passage, with reduced drug level in the peripheral blood plasma relative to the dose given. This may explain the apparent diminution of side-effects following i.a.h. CDDP treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Kidney Diseases; Leucovorin; Liver; Liver Neoplasms; Methotrexate; Neoplasms; Nervous System Diseases; Ovarian Neoplasms; Remission Induction; Spectrophotometry, Atomic; Tumor Cells, Cultured; Vinblastine

Circadian (about 24 h) changes modulate cellular metabolism and proliferation in healthy tissues. As a result, the extent of toxicity of cancer chemotherapy varies by 50% or more according to dosing time in mice or rats. These experimental data led to test the principle of adapting chemotherapy delivery to circadian rhythms--so-called "chronotherapy"--in cancer patients. Clinical trials first aimed to assess toxicities and maximal tolerated dose of chronotherapy schedules. Programmable-in-time pumps became the indispensable tool for reliably testing this principle in a large enough patient population and without any need for hospitalization. Results from randomized clinical trials have indicated that chronotherapy allowed to increase dose intensity (DI, a secondary criterion in these trials) by 13 to 45% as compared to injecting the drug at another time (doxorubicin, cisplatin) or according to a flat rate (5-fluorouracil, floxuridine, oxaliplatin). A non-randomized trial further suggested this principle would also apply to cytokine delivery (interferon alpha). Two consecutive randomized trials have revealed that chronotherapy-related increase in 5-FU DI was further associated with a 20% increase in response rate of patients with metastatic colorectal cancer to the 3-drug association that was used (5-FU, folinic acid and oxaliplatin). In a subsequent phase II trial 5-FU daily dose and 3-drug treatment frequency were increased in 50 patients with this disease. Such intrapatient dose escalation protocol also disclosed a positive correlation between DI of 5-FU and response. New anticancer drugs should benefit from this approach so that both their clinical safety and patient's quality of life are improved, through ambulatory administration.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chronobiology Phenomena; Circadian Rhythm; Cisplatin; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Floxuridine; Fluorouracil; Humans; Infusion Pumps; Interferon-alpha; Leucovorin; Male; Mice; Neoplasms; Neoplasms, Experimental; Organoplatinum Compounds; Ovarian Neoplasms; Oxaliplatin; Rats

The purpose of this study was to estimate the response rate, response duration, and survival of patients with advanced ovarian cancer treated with a 132-hr continuous infusion of high-dose calcium leucovorin in combination with five consecutive daily bolus doses of 5-fluorouracil (5-FU) and to correlate changes in CA-125 levels with clinical and radiologic assessment of disease progression. Forty-six heavily pretreated patients [median number of previous chemotherapy regimens, 2.5 (range 1-7)] with advanced ovarian cancer received 132-hr continuous infusions of calcium leucovorin (500 mg/m2/day) for 5 1/2 days, with daily bolus doses of 5-FU (370 mg/m2/day) for 5 days beginning 24 hr after initiation of the calcium leucovorin. Twenty-three patients had clinically measurable disease and 23 had evaluable disease; CA-125 levels were performed prior to each treatment course and after the final course of therapy. One of 42 patients had a partial response to combination chemotherapy (duration, 8.9 months); 16/42 had stable disease [median duration, 4.9 months (range, 2.4-9.0 months)]. Toxicity of combination therapy included mild myelosuppression and stomatitis, similar to previously reported toxicity profiles for the 5-FU and calcium leucovorin combinations. Sensitivity of CA-125 levels as a single indicator of disease progression was 55%. The combination of infusional high-dose calcium leucovorin and 5-FU has little activity in refractory ovarian cancer. CA-125 levels incorrectly predict clinical disease activity in about one-third of cases and should not be the sole criterion for determination of clinical response when evaluating chemotherapeutic efficacy in heavily pretreated patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; CA-125 Antigen; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Ovarian Neoplasms; Sensitivity and Specificity

In this series 49 patients with epithelial ovarian carcinoma previously treated with platinum-based chemotherapy received leucovorin 200 mg/m2 i.v. bolus followed by 5-fluorouracil at 370 mg/m2 i.v. bolus daily for 5 days every 4 weeks for the first two courses and subsequent courses were given every 5 weeks. Of this group, 47 patients were evaluable for toxicity and 44 for response. Of the patients evaluable for response, 15 were considered platinum-sensitive and 29 were platinum-refractory. The overall response rate was 6/44 (13.6%). There were two complete responders (4.5%) and four partial responders (9.1%). In the platinum-sensitive patients, there was one complete response, yielding a response rate of 6.6%, whereas in the platinum-refractory patients, there were four partial responses and one complete response for a response rate of 17.2%. Five responses were in the pelvis and there was one response at an extrapelvic site in the abdominal mesentery. The median number of courses delivered was three (range: 1-10). The major adverse effect was myelosuppression with 16/47 (34.0%) experiencing granulocytopenia < 1,000/mm3. The median white blood count nadir for the patients experiencing any leukopenia was 2,700 (range: 400-3,900/mm3). There was one episode of grade 3 thrombocytopenia. Grade 3 intestinal toxicity was seen in seven patients (14.9%). There were no treatment-related deaths. In this previously treated population, 5-fluorouracil with high-dose leucovorin exhibited activity of interest in the platinum-refractory population and warrants further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Drug Resistance; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Treatment Outcome

Thirty-nine women with advanced, recurrent epithelial ovarian carcinoma who failed prior treatment with a platinum-based regimen were treated with leucovorin, 20 mg/m2 intravenously followed by 5-fluorouracil, 425 mg/m2 intravenously, daily for 5 consecutive days every 5 weeks in a phase II trial. Partial regressions were seen in 3 of 15 (20%) measurable disease patients, and objective regressions were seen in 3 of 14 (21%) evaluable/nonmeasurable disease patients. A 50% or greater decrease in CA-125 level was observed in 3 of 10 (30%) patients with no objectively evaluable or measurable disease. Overall objective response rate was 23% (95% confidence interval: 11 to 39%) in all 39 patients evaluated, with a median time to progression of 3 months and overall median survival of 7 months. Toxicities were acceptable and consisted of neutropenia, thrombocytopenia, stomatitis, and mild diarrhea. 5-Fluorouracil, as administered in this protocol, had modest antitumor activity in cisplatin-refractory ovarian carcinoma of short duration and minimal toxicity.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Female; Fluorouracil; Humans; Injections, Intravenous; Leucovorin; Middle Aged; Ovarian Neoplasms

Twenty-one patients with recurrent epithelial ovarian carcinoma not amenable to cure with further surgery or radiotherapy were entered into a Phase II trial utilizing i.v. leucovorin at 20 mg/m2 followed by i.v. 5-fluorouracil at 425 mg/m2 administered daily for 5 days every 4 weeks for the first two courses and then every 5 weeks. Twenty-one patients were entered. Of these, 20 were eligible for toxicity assessment and 19 for response. Five had received prior radiotherapy, and all had received prior cisplatin-based chemotherapy. There was one patient response (5.3%; 95% confidence intervals for response of 0% to 26%). Toxicity was moderate with 5 of 20 (25%) grade 3 or 4 leukopenia, 12 of 20 (60%) grade 3 or 4 granulocytopenia, 1 of 20 (5%) grade 3 thrombocytopenia, 5 of 20 (25%) grade 3 GI toxicity, and 2 of 20 (10%) grade 3 neurotoxicity. There was one toxic death in a patient who developed granulocytopenia and pneumonia after her third course of treatment. This dose schedule of 5-fluorouracil and leucovorin has minimal activity in patients with recurrent epithelial ovarian carcinoma who have received prior cisplatin chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Ovarian Neoplasms; Recurrence

Twenty patients with documented progression after two or three cisplatin-based regimens for advanced epithelial ovarian carcinoma were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. One clinically complete and two partial responses were observed in 16 evaluable patients, with 5 remaining stable. Median survival was 9 months. Toxicity was mild. This combination achieved a 19% (95% confidence interval 4%-46%) response rate in heavily pretreated cisplatin-resistant patients.

Topics: Aged; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Ovarian Neoplasms

This report compares long-term survival rates for patients treated with four different chemotherapeutic regimens for Stages III and IV ovarian adenocarcinoma. The patients were entered into consecutive, prospective, randomized studies with an essentially common chemotherapeutic arm. The first study compared the single agent melphalan with actinomycin D, 5-fluorouracil, and Cytoxan. The second study compared 5-fluorouracil plus Cytoxan and methotrexate-leucovorin rescue plus Cytoxan. The patient characteristics in the two studies were very similar except for more aggressive tumor-reductive operations in the second study. Observed survival rates for the first 2 years in the second study were very much higher than in the first study. However, by the third, fourth, and fifth years, the survival rates of the 5-fluorouracil-Cytoxan-treated individuals had reached the same low levels seen in the first study. It appears that an optimum surgical procedure by itself may enhance survival during the first 2 years. Survival with methotrexate-leucovorin rescue plus Cytoxan was statistically significantly better than with melphalan or actinomycin D-5-fluorouracil-Cytoxan. Third-, fourth-, and fifth-year survival rates with methotrexate-leucovorin rescue plus Cytoxan were substantially higher than with 5-fluorouracil-Cytoxan; however, the survival distributions for these two treatments were not statistically significantly different. Long-term survival rate data for patients with Stages III and IV ovarian adenocarcinomas treated with chemotherapy are rare. The 19% 5-year survival rate with methotrexate-leucovorin rescue plus Cytoxan in the present study is considerably higher than other reported survival rates.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Cystadenocarcinoma; Dactinomycin; Female; Fluorouracil; Humans; Leucovorin; Methotrexate; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Ovary; Prognosis; Prospective Studies; Random Allocation; Time Factors

Thirty-three patients with advanced-stage ovarian adenocarcinomas, with no prior chemotherapy, were treated with weekly cisplatin (DDP) for four courses followed by five monthly courses of one of two randomly assigned multidrug combinations. These combinations were high-dose methotrexate-leucovorin plus cyclophosphamide (MECY) or cyclophosphamide, hexamethylmelamine, doxorubicin, and DDP (CHAD). Patients with no clinically measurable disease after 6 months of therapy were evaluated by laparoscopy. In the absence of disease progression at the time of the laparoscopy the study design called for a repeat cycle of four weekly DDP courses and another five monthly courses of the assigned multidrug combination. All patients with no evidence of disease after 1 year of treatment had a second-look laparoscopy which, if negative, was followed by a second-look laparotomy. This report includes all of the consecutively entered patients observed for a minimum of 1 year or to death. DDP-MECY and DDP-CHAD were similarly active for overall response rates and complete response rates according to laparoscopic criteria. However, DDP-MECY had a statistically significantly lower relapse rate (P less than 0.02) and a statistically significantly higher negative second-look laparotomy rate than did DDP-CHAD. Using all entered patients, with no exclusions from analysis, eight of 17 patients (47%) treated with DDP-MECY had negative second-looks after 1 year of treatment. This compares with one of 16 (6%) negative second-looks in patients treated with DDP-CHAD (P less than 0.02). The high negative second-look rate with DDP-MECY is exciting. Positive cytologic washings at the 6-month laparoscopic evaluation were highly predictive that residual disease would be found at the 1-year second-look surgery. Only one patient with positive peritoneal cytology after 6 months of treatment was found to have a negative second-look after 1 year of therapy.

Topics: Adenocarcinoma; Altretamine; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Methotrexate; Neoplasm Staging; Ovarian Neoplasms

In a prospective randomized study, the chemotherapeutic combination of high-dose methotrexate-citrovorum factor rescue plus cyclophosphamide (MECY) has been shown to be statistically significantly superior to the combination of 5-fluorouracil plus cyclophosphamide (FUCY) in the treatment of Stage III-IV ovarian adenocarcinoma. With MECY, an overall objective remission rate of 67% and a complete remission rate of 48% were achieved. All patients had undergone no treatment except for surgery. In addition to the chemotherapy, patients were randomly allocated to receive or not receive nonspecific immunotherapy with Corynebacterium parvum; this immunotherapy had no apparent effect on the chemotherapeutic response. The study demonstrates a high degree of activity for the MECY regimen, and a comparison between the results with MECY in this study and melphalan in an earlier prospective randomized study provides statistical evidence favoring MECY over single-agent melphalan in the treatment of this disease.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Bacterial Vaccines; Child; Clinical Trials as Topic; Cyclophosphamide; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Ovarian Neoplasms; Propionibacterium acnes; Prospective Studies

Topics: Adult; Aged; Carcinoma, Squamous Cell; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Ovarian Neoplasms; Vincristine

High-dose methotrexate with leucovorin rescue plus cyclophosphamide resulted in a 66.6% objective response rate with a 50% complete response rate. These preliminary results are higher than our previous results with melphalan alone or actinomycin D, 5-fluorouracil, and cyclophosphamide in women with advanced ovarian adenocarcinoma. Circulating ovarian cystadenocarcinoma-associated antigen serum levels were positive in 69.8% of patients and correlated with response to chemotherapy in 70% of patients. To date, all of the patients with advanced ovarian adenocarcinoma were found to have elevated galactosyltransferase levels. Galactosyltransferase levels correlated with response to therapy in the first five patients followed serially.

Topics: Adenocarcinoma; Antigens, Neoplasm; Antineoplastic Agents; Clinical Trials as Topic; Cyclophosphamide; Drug Therapy, Combination; Female; Galactosyltransferases; Humans; Leucovorin; Methotrexate; Ovarian Neoplasms

45 patients (43 ovarian carcinoma and 2 chorionepithelioma) were treated with high doses of methotrexate and intramuscularly application of leucovorin according to Mathé et al. In comparison a group of 19 patients (ovarian carcinoma only) was treated with methotrexate and leucovorin-tablets. The toxic effects on leucocytes and platelets were equal in both groups. Due to slightly different doses of leucovorin in both groups an enteral resorption rate of more than 90 p.c. is calculated. Because of the simple way of application the suggested high-dose therapy with methotrexate and leucovorin-tablets seems to be most convenient in the moment.

Topics: Administration, Oral; Blood Platelets; Choriocarcinoma; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Leucovorin; Leukocytes; Methotrexate; Middle Aged; Ovarian Neoplasms; Pregnancy

In a randomized study, 35 patients with advanced-stage epithelial ovarian cancers with progressive disease after prior single alkylating agent or combination-agent chemotherapy were treated with either intermediate high-dose methotrexate-citrovorum factor rescue alone or methotrexate-citrovorum factor rescue plus cyclophosphamide. Objective responses to both "second-line" chemotherapeutic regimens were observed. The objective response rate of 43% observed with the methotrexate-citrovorum factor plus cyclophosphamide treatment was superior to that achieved with methotrexate-citrovorum factor given alone. This combination of agents is the most effective second-line chemotherapeutic regimen for ovarian cancer that we have yet tested and we are therefore optimistic about its possibilities as first-line therapy. After early dosage modifications, serious toxic side effects were rare in this group of patients who had had extensive prior therapy.

Topics: Adult; Aged; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Ovarian Neoplasms

Cytoreductive surgery including liver resection and hyperthermic intraperitoneal chemotherapy provide survival benefit to selected patients but is associated with relevant morbidity and mortality rates. We aimed to report morbidity and mortality rates and parameters linked to increased morbidity.. Retrospective analysis of 37 patients who underwent liver resection and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy between 2006 and 2016. From a prospectively collected database the morbidity and mortality rates and survival data were analyzed.. The mortality rate was 0% and grade III-IV morbidity was 42%. Re-operation rate was 27%. Patients with complications tended to have a higher peritoneal cancer index (16 vs. 13; P=0.23). The performance of rectal resections was statistically significantly associated with morbidity (P=0.02). Neither performance of other type of resections nor the hyperthermic intraperitoneal chemotherapy compound nor the completeness of cytoreduction score was associated with elevated morbidity. No complications related to liver resections were observed. Furthermore, origin of peritoneal metastases did not impact on occurrence of complications. Median overall survival for colorectal primaries was 22 months (range, 9-60 months) and 30 months (range, 12-58 months) for ovarian cancer.. Simultaneous resection of hepatic and peritoneal metastases seems to provide a survival benefit for selected patients and is associated with acceptable morbidity and mortality rates. Knowledge of patients and operative factors linked to morbidity will help to provide a strict selection process and a safer surgical procedure.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Female; Fluorouracil; Hepatectomy; Humans; Hyperthermia, Induced; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies

Bevacizumab (bev), when added to a moderate dose combination of previously failed cytotoxins, as a third- and fourth-line therapy for refractory gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality responses. The regimen was based on preclinical models designed in order to simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic drugs.. Induction treatment was free of life-threatening complications. Nine consecutive patients, 3 under second- and 6 under multi-line treatment, had 9 objective responses and 8 produced long clinical benefits, 2 of which were complete responses. Seven responses created opportunities for personalized added treatment and research. Absolute median survival was 21.5 months for the 8 patients with platinum-resistant tumors. One patient was unable to tolerate a first standard adjuvant dose of paclitaxel. After rapid peritoneal progression of disease, treatment has produced 52+ months of unmaintained complete remission.. Bev, in the combination that was used in this study, meets response, survival, and toxicity criteria for further testing against second- or multi-line chemotherapy-resistant tumors and also when a standard treatment is not safe.

Topics: Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bile Duct Neoplasms; Camptothecin; Cholangiocarcinoma; Cisplatin; Deoxycytidine; Docetaxel; Endometrial Neoplasms; Female; Fluorouracil; Gemcitabine; Humans; Induction Chemotherapy; Irinotecan; Leucovorin; Middle Aged; Ovarian Neoplasms; Retrospective Studies; Taxoids

MMR-D pancreatic cancer have been reported to respond to checkpoint inhibitor therapy. Here, we report the first case of acquired resistance to immunotherapy in MMR-D pancreatic cancer.. A 45-year-old woman with unresectable MMR-D pancreatic cancer was initially treated with FOLFIRINOX, FOLFIRI, and stereotactic body radiation with stable disease burden. After 3 months, imaging showed progression of disease with an increase in CA19-9. She was subsequently enrolled in a clinical trial of an anti-PD-L1 antibody in combination with an IDO1 inhibitor. She demonstrated a partial response to therapy by RECIST 1.1 criteria with declining tumor markers. Twenty-two months after beginning immunotherapy, imaging revealed an increasing left ovarian cystic mass. There were no other sites of progressive disease. The patient underwent a total hysterectomy and bilateral salpingo-oophorectomy, appendectomy, omentectomy and pelvic lymphadenopathy. Pathology was consistent with a metastasis from the pancreas involving the endometrium and left ovary. Thereafter, the patient continued with PD-1 blockade therapy off protocol with no further progressive disease. Immune profiling showed high levels of CD8+ T cells and PD-1 positive immune cells infiltrating the tumor, with a moderate level of PD-L1 expression in both the immune cells and the tumor cells. Next generation sequencing found only the KRAS G12D and RNF43 G659Vfs*41 mutations were retained from the pre-treatment tumor in the treatment-resistant tumor.. This is the first report describing acquired resistance to immunotherapy in MMR-D pancreatic cancer with accompanying genomic and immune profiling. This case of oligoprogression in the setting of immunotherapy demonstrates the feasibility of localized treatment followed by continuation of immunotherapy to sustain ongoing response.

Topics: Adenocarcinoma; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Camptothecin; Drug Resistance, Neoplasm; Endometrial Neoplasms; Female; Fluorouracil; Humans; Immunotherapy; Indoleamine-Pyrrole 2,3,-Dioxygenase; Irinotecan; Leucovorin; Middle Aged; Ovarian Neoplasms; Oxaliplatin; Pancreatic Neoplasms

A 71-year-old female patient underwent urgent laparotomy due to severe right lower quadrant abdominal pain and fever. Macroscopically duplex coecal and transverse colon cancer as well as a sigmoid or left ovarian cancer were suspected. Pathological findings revealed synchronous left ovarian and transverse colonic neoplasms. Both primaries metastatized to their regional lymph nodes. Furthermore, the ovarian cancer infiltrating the sigmoid colon gave distant metastasis in the coecum, too. Ovarian cancer histology showed papillary adenocarcinoma, and transverse colon cancer was a tubular adenocarcinoma. The affected lymph nodes were clearly distinguished by immunohistochemistry staining: ovarian metastases were CK7 positive, and colonic metastases were CK20 and CEA positive. The patient was treated with combinated chemotherapy: FOLFOX-4 two weekly and paclitaxel monotherapy every other week. The patient tolerated this combined treatment well. The authors conclude that multiple synchronous neoplasms can be treated with individualized chemotherapeutic protocol with good efficacy and few adverse reactions.

Topics: Abdominal Pain; Adenocarcinoma; Adenocarcinoma, Papillary; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Colonic Neoplasms; Drug Administration Schedule; Female; Fever; Fluorouracil; Humans; Immunohistochemistry; Keratin-20; Keratin-7; Laparotomy; Leucovorin; Lymphatic Metastasis; Neoplasms, Multiple Primary; Organoplatinum Compounds; Ovarian Neoplasms; Paclitaxel; Precision Medicine; Treatment Outcome

Colon cancer in pregnancy is uncommon. Only a small number of case reports have been published in the literature on the use of chemotherapeutic drugs during pregnancy. Reports of such cases assist clinicians in further investigating the use of chemotherapy in pregnancy.. FOLFOX-6 was administered to a pregnant, 33-year-old Saudi woman with metastatic colon cancer from 22 to 30 weeks of gestation. Her cancer was diagnosed during her pregnancy. She tolerated the chemotherapy well and delivered a full-term baby girl with no obvious harm, and normal development was documented at her 2-year follow-up examination.. Colon cancer during pregnancy is not easily detected and is difficult to manage. A detailed history and high clinical suspicion are needed in patients who present with symptoms and signs suggestive of malignancy. A multidisciplinary approach with patient involvement is needed to decrease morbidity and mortality caused by both treatment and the cancer in the mother and to limit side effects for the fetus. Further data and long-term follow-up are needed to better understand the potential long-term side effects of chemotherapeutic drugs on offspring.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Ovarian Neoplasms; Ovariectomy; Oxaliplatin; Pregnancy; Pregnancy Complications, Neoplastic

Women suffering from recurrent platinum-resistant ovarian carcinoma go through several lines of chemotherapy, but eventually fail all conventional chemotherapy options. After failing multiple other regimens, we offer patients fluorouracil (5-FU) in a weekly regimen with leucovorin. For those women who failed to react to multiple lines of treatment, 5-FU has been shown to be a reasonable option with reported response rates of 10% to 33%. We report our experience with 5-FU+leucovorin in this patient population.. This is a retrospective chart review of women treated for recurrent ovarian carcinoma between January 2003 and December 2009. Women with recurrent ovarian carcinoma who had been treated with at least 3 previous chemotherapy regimens and had received 5-FU were eligible for the study. 5-FU and leuocovorin are given at 600 mg/m weekly for 6 weeks of an 8-week cycle. Patient charts were reviewed for demographics and disease history relevant to the administration of 5-FU. Response was assessed clinically and by CA125 levels.. Fifty-three patients matching inclusion criteria received 5-FU during the study period. Twenty-five percent of patients achieved a partial response and 17% stable disease for an overall response rate of 42%. A median of 4 weekly doses was administered (range, 1 to 26). The median survival of the whole cohort was 10 weeks after the last dose of 5-FU was administered.. In this population of heavily pretreated patients, a significant response to 5-FU can be achieved. Unfortunately, the response is short lived and mostly partial.

Topics: Adenocarcinoma, Mucinous; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Papillary; Cystadenocarcinoma, Serous; Endometrial Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Retrospective Studies; Survival Rate

The development of ovarian metastases from gastric cancer indicates a turning point of the disease progression and is usually associated with poor prognosis. Efficacy of modern chemotherapy protocols in ovarian metastases from gastric cancer is unknown. In this case series, we have evaluated the chemosensitivity of ovarian metastases from gastric cancer in eight consecutive patients treated in our institution between January 2000 and April 2012. Median age at gastric cancer diagnosis was 48.3 years and ovarian metastases were mainly metachronous (88%). Patients were treated with FOLFOX or FOLFIRI protocols in first-line and with EOX protocol in second-line chemotherapy. These protocols of chemotherapy used in first- and second-line treatment were able to control the disease in 33.3% for ovarian metastases compared to 66.7% for extraovarian metastases. Mean overall survival (OS) from ovarian metastases diagnosis was 14.2 months. The four patients treated by bilateral oophorectomy had a longer mean OS (16 months) than the four patients who did not experienced surgery (12.3 months). In conclusion, this case series suggests that ovarian metastases from gastric cancer are less sensitive than extraovarian metastases to modern protocol of chemotherapy. To confirm these observations, a large retrospective study is ongoing.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Ovariectomy; Stomach Neoplasms

A 50-year-old woman was diagnosed with ascending colon cancer with bilateral ovarian metastases, carcinomatous peritonitis, and carcinomatous pleurisy. Nine courses of mFOLFOX6 treatment resulted in the disappearance of her ascites and pleural effusion and a marked decrease in her serum CEA and CA19-9 levels. Additionally, the primary tumor and ovarian metastases became smaller. Therefore, a right hemicolectomy with D3 lymph node dissection, total hysterectomy, and bilateral salpingo-oophorectomy were performed. Postoperatively, we changed the chemotherapy from mFOLFOX6 to bevacizumab+FOLFIRI because the patient had an allergic reaction to oxaliplatin, and we suspected lung metastasis. Because the lung metastasis grew after ten courses of bevacizumab+FOLFIRI, we changed to cetuximab+FOLFIRI. Unfortunately, 28 months after her diagnosis, the patient died of carcinomatous pleurisy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Fatal Outcome; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoplasm Grading; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms

A 44-year-old female was referred to our hospital with a complaint of abdominal fullness. Computed tomography(CT) showed multiple liver masses and a huge ovarian tumor. Colonoscopy revealed a type 4 advanced cancer in the sigmoid colon. She was diagnosed with unresectable liver and ovarian metastases from advanced sigmoid colon cancer, for which we were obliged to select chemotherapy. As the first line, FOLFOX was applied and performed for 6 cycles, followed by FOLFOX plus bevacizumab(BV)for 5 cycles. While no deterioration of liver and ovarian metastases was observed during the course of those chemotherapy regimens, the patient developed a considerable level of acute sensorimotor neuropathic symptoms associated with oxaliplatin-induced peripheral neurotoxicity, forcing us to replace FOLFOX plus BV with FOLFIRI plus BV. Three cycles of FOLFIRI plus BV, however, turned out to be progressive disease with deterioration of liver and ovarian metastases. Since her oxaliplatin-induced neurotoxicity was improved, a regimen of FOLFOX plus BV was once again applied to her for 3 cycles, which failed to prevent her from having a progressive disease. The sequencing of K-RAS genes from the biopsy specimens of sigmoid colon cancer revealed an expression of a wild-type K-RAS. Thus, an addition of panitumumab to FOLFOX was made. Surprisingly, after 3 cycles of the chemotherapy regimen over 3 months, a significant reduction in the size of liver and ovarian metastases was observed. Her sense of abdominal fullness was apparently reduced and was even lower than what it was at admission. Panitumumab has great potential for effective treatment of patients with unresectable stage IV colorectal cancer, even after having acquired resistance to prior chemotherapy regimens.

Topics: Adult; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Ovarian Neoplasms; Panitumumab; Sigmoid Neoplasms

Thrombotic microangiopathy occurs in 5-10% of patients with mucin-producing disseminated adenocarcinoma. A 28-year-old woman complained of fatigue, bone pain, and weight loss. There were pallor, icterus, and tenderness in the bones on physical examination. Microangiopathic hemolytic anemia, leukoerythroblastic picture, thrombocytopenia, and normal coagulation tests were detected. Thrombotic thrombocytopenic purpura (TTP) was diagnosed and therapeutic plasma exchange was performed on the patient. On day 5 a laparotomy had to be performed because of acute abdomen due to the rupture of a corpus hemorrhagicum follicle of an ovary. Signet ring cell adenocarcinoma stained with cytokeratin 7 and mucicarmine was seen on ovaries and bone marrow, after the pathological examination. The primary site of tumor could not be investigated, because of the patient's refusal. Although chemotherapy including cis-platinum, infusional 5-fluorouracil, and calcium leucovorin were administered in two courses, she died from respiratory failure. In conclusion, malignancy and bone marrow involvement should be considered when associated with leukoerythroblastic picture and TTP.

Topics: Abdomen, Acute; Adenocarcinoma, Mucinous; Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Marrow Neoplasms; Carcinoma, Signet Ring Cell; Cisplatin; Fatal Outcome; Female; Fluorouracil; Hemoperitoneum; Humans; Laparotomy; Leucovorin; Neoplasms, Unknown Primary; Ovarian Neoplasms; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Respiratory Insufficiency

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cystadenocarcinoma, Mucinous; Female; Fluorouracil; Gynecologic Surgical Procedures; Humans; Leucovorin; Neoplasm Staging; Organoplatinum Compounds; Ovarian Neoplasms; Practice Guidelines as Topic; Prognosis

This pilot clinical trial explored the feasibility, safety, and efficacy of regional hepatic therapy combined with systemic anticancer agents in patients with refractory solid tumors and extensive unresectable liver involvement, including those with compromised hepatic function.. Six patients with colorectal (N = 3), ovarian (N = 2), and hepatocellular carcinoma (N = 1) received intra-arterial hepatic oxaliplatin followed by intravenous 5-fluorouracil, leucovorin, and bevacizumab every 2 weeks until disease progression. All had extensive liver metastases; four had elevated baseline serum total bilirubin. Median total bilirubin was 2.8 mg/dL (range, 0.2-5.2 mg/dL). Median Child-Pugh score was 7 (range, 5-10).. Thirty treatments were delivered (2-7 per patient). Median age of patients was 57 years (range, 25-69 years). Three patients (1 with colorectal, 1 with hepatocellular, and 1 with ovarian cancer) attained partial responses. Two had failed previous oxaliplatin and cisplatin treatment. Some with elevated bilirubin at baseline had a significant drop in bilirubin with treatment (bilirubin 5.2 → 1 mg/dL, 4.8 → 1.1 mg/dL, and 5.2 → 1.8 mg/dL). The regimen was generally well tolerated; the most common side effects were grade 1 fatigue, anorexia, and/or hypertension. One patient died of enzyme-linked, immunoassay-confirmed, heparin-induced thrombocytopenia during the sixth cycle of therapy.. At doses tested, this regimen was safe and demonstrated antitumor activity in patients with advanced refractory malignancies involving the liver, including those with hepatic insufficiency. Further study is warranted.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Resistance, Neoplasm; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Oxaliplatin; Pilot Projects; Salvage Therapy; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome

This is an account of a case of primary adenocarcinoma of the small intestine with peritoneal dissemination successfully treated with chemotherapy. A 64-year-old woman was admitted with a complaint of severe abdominal distension. Abdominal computerized tomography revealed a bowel obstruction with tumor and the remarkable small bowel dilation of oral side of tumor. The tumor was found at surgery to be at the ileum 15 cm proximal from the ileocecal region. Peritoneal dissemination was recognized around the ileocecal region, so ileum partial resection was performed for the primary cancer lesion and dissemination region. Pathological diagnosis of the resected specimen was adenocarcinoma with lymph nodes metastasis. The peritoneal dissemination consisted of metastatic adenocarcinoma from small intestine. After an operation, internal use of S-1 was performed as adjuvant chemotherapy. But a recurrent lesion at the ovarium was detected 6 months after surgery. The patient was subsequently treated with resection of the ovarium. For lung metastasis, the combination chemotherapy with mFOLFOX6 + bevacizumab was administered. Primary small intestinal adenocarcinoma is a rare disease, and it is often diagnosed as advanced cancer because of few characteristic symptoms. So carcinoma of the small intestine usually has a poor prognosis.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; Humans; Ileal Neoplasms; Intestinal Neoplasms; Leucovorin; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Oxonic Acid; Tegafur

Malignant transformation in a mature cystic teratoma of the ovary is rare. The most common malignancy is squamous cell carcinoma, which consists of about 75% of malignant transformations. In the present report, we describe a case of advanced-stage squamous cell carcinoma arising in a mature cystic teratoma. A postmenopausal 63-year-old woman with squamous cell carcinoma arising in a mature cystic teratoma is presented. The initial investigation by ultrasound showed a left adnexal mass with mixed echo pattern, which arose the suspension of malignancy. She underwent a laparotomy and left oophorectomy. Histopatholog was compatible with squamous cell carcinoma arising in a mature cystic teratoma. After a few episodes of intestinal obstruction and colostomy, she underwent partial resection of the ileum and sigmoid colon four months after the initial oophorectomy. Histopathologic study showed metastatic poorly-differentiated squamous cell carcinoma. Subsequently, she underwent two courses of combination chemotherapy with cisplatin, leucovorin, and 5-fluorouracil with no response. She died from progression of the disease nine months after the initial operation.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Colostomy; Fatal Outcome; Female; Fluorouracil; Humans; Ileal Neoplasms; Intestinal Obstruction; Leucovorin; Middle Aged; Neoplasms, Multiple Primary; Ovarian Neoplasms; Ovariectomy; Sigmoid Neoplasms; Teratoma; Ultrasonography; Vitamin B Complex

The patient was a 41-year-old female, who underwent histectomy and sdnexopexy due to perforated ovarian tumor. One month later, she was diagnosed with simultaneous bilateral metastatic ovarian tumor of colon cancer, and right hemicolectomy (D3) was performed. After surgery, the patient was treated with 10 courses of therapy with the FOLFOX4 regimen. No recurrence was recognized, and the patient was treated with 12 courses of therapy with oral tegafur/ uracil (UFT)+oral Leucovorin (LV). The patient evidenced no tumor recurrence 2 years after the initial treatment. We consider oral UFT+oral LV therapy was useful for post FOLFOX4 therapy after R0 surgery.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Colectomy; Colonic Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Ovarian Neoplasms; Tegafur; Uracil; Vitamin B Complex

We report a case of ovarian metastasis after complete response of colon cancer. A 55-year-old woman underwent a sigmoidectomy for sigmoid colon cancer with hepatic metastasis and para-aorta lymph node metastasis. After the operation, the patient was given chemotherapy with bevacizumab+mFOLFOX6. Nine months after the operation, the patient was judged to have achieved complete response. Thirteen months after the operation, right ovarian tumor was found and bilateral oophrectomy, hysterectomy and omentectomy were performed. Histopathologically the ovarian tumor was metastasized from colonic cancer. After the second operation, the patient was given chemotherapy with bevacizumab+FOLFIRI. At present, the patient remains disease-free for 6 months after the ovarian operation.

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colonic Neoplasms; Female; Fluorouracil; Humans; Hysterectomy; Leucovorin; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Ovariectomy

A 56-year-old woman diagnosed with a poorly differentiated cecal adenocarcinoma with metastases to ovaries, omentum, and sigmoid colon went into remission after 12 cycles of infusional 5-fluorouracil, luecovorin, and oxaliplatin (FOLFOX-4 regimen). Thirteen months later, a pelvic recurrence was diagnosed, and the patient received nine cycles of FOLFOX-6 plus bevacizumab, resulting in a clinical complete response but the development of pancytopenia. Bone marrow biopsy was consistent with therapy-related acute myelogenous leukemia. Chromosome analysis showed structural rearrangements with partial deletions of the long arms of chromosomes 5, 7, 20, and 21, as well as trisomy of chromosome 8 and losses of chromosomes 3 and 11. Induction chemotherapy led to remission, but the patient died two months later from complications of colon cancer progression. It is likely that the leukemia was related to the oxaliplatin administration.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cecal Neoplasms; Chromosome Deletion; Female; Fluorouracil; Humans; Leucovorin; Leukemia, Myeloid, Acute; Middle Aged; Omentum; Organoplatinum Compounds; Ovarian Neoplasms; Peritoneal Neoplasms; Sigmoid Neoplasms; Trisomy

Topics: Antineoplastic Combined Chemotherapy Protocols; CA-125 Antigen; Female; Fluorouracil; Humans; Leucovorin; Organoplatinum Compounds; Ovarian Neoplasms; Oxaliplatin

A 58-year-old woman underwent surgery for a pelvic mass. Palliative resection was performed despite the presence of multiple retroperitoneal lymph nodes. All pathology specimens exhibited an adenocarcinomatous component associated with carcinoid proliferation related to an appendicular tumor leading to the diagnosis of appendicular adenocarcinoid with ovarian, peritoneal, and nodal metastases. The patient's general status worsened rapidly with widespread nodal metastasis. Chemotherapy (Folfox 4 regimen) was given, and the patient improved within six weeks. Complete response was achieved after three months. Presently, more than three years after the end of the treatment, the patient is still alive and in complete remission. Appendicular adenocarcinoid is exceptional. These tumors exhibit two cellular components. Ovarian metastasis is frequent. Prognosis is intermediate between adenocarcinoma and malignant carcinoid. When given to patients with colonic carcinoma, the Folfox regimen used effectively here, is associated with a 50% objective response but complete response is very exceptional.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lymphatic Metastasis; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Ovarian Neoplasms

To describe our experience with malignant ovarian germ cell tumors with special reference to reproductive performance after remission, medical records of 31 patients were reviewed. The mean age at diagnosis was 18.6 years. Tumor by stage was I in 16 cases, II in 5, III in 5, IV in 3, and recurrence in 2. Histology was dysgerminoma in 7 cases, yolk sac tumor in 10, immature teratoma in 7, choriocarcinoma in 1, and mixed-type tumor in 6. Conservative surgery for fertility preservation was performed in 21 cases. Postoperative chemotherapy was given to all cases except two with stage Ia dysgerminoma. Of 31 cases, 4 including one fertility-preserved case died of disease. The other 27 cases including 20 fertility-preserved cases were successfully treated. Twenty-five cases (92.6%) have been followed longer than 60 months and 13 cases (48.1%) longer than 120 months. By the last follow-up, 8 of the 20 fertility-preserved cases delivered a total of 9 normal babies. Of the remaining 12 nonpregnant cases, 3 married, 9 have had regular menses, and 3 have had menstrual problems. Two of the latter three cases have been in hypergonadotropic anovulatory cycles. One patient has been diagnosed with tubal infertility caused by peritubal adhesion. Thus, management of the disease with fertility preservation is safe and the majority of patients can attain or retain normal ovarian function and reproductive potential.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Cisplatin; Cyclophosphamide; Dactinomycin; Doxorubicin; Dysgerminoma; Endodermal Sinus Tumor; Etoposide; Female; Fertility; Follow-Up Studies; Germinoma; Humans; Leucovorin; Menstruation; Methotrexate; Ovarian Neoplasms; Remission Induction; Reproduction; Vincristine

Ovarian metastasis may present at the time of initial diagnosis of colon carcinoma or as a later recurrence. Little meaningful information is available regarding the treatment and outcome of synchronous ovarian metastasis of colon carcinoma. This report describes the clinical course of five patients with synchronous ovarian metastasis of colon carcinoma who were treated with aggressive surgery and chemotherapy. The treatment consisted of maximal surgical debulking followed by systemic chemotherapy with weekly 24 h infusion of high-dose 5-fluorouracil and leucovorin. All of the five patients had subsequent disease-free periods ranging from 6 to 43+ months following operation. Two of the patients who had no or minimal peritoneal involvement were still alive without disease at 33 and 43 months. The data from these cases suggest that aggressive surgery and systemic chemotherapy may be highly efficacious in the treatment of colon carcinoma with synchronous ovarian metastasis. Maximal debulking followed by chemotherapy may be particularly effective in those patients with minimal peritoneal involvement.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Colonic Neoplasms; Combined Modality Therapy; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Middle Aged; Ovarian Neoplasms

The objective of this study was to evaluate the activity of the combination of 5-fluorouracil (5-FU) and leucovorin in women with platinum-resistant recurrent or advanced ovarian cancer. A retrospective study was conducted of consecutive patients treated with weekly intravenous 5-FU and leucovorin, both at 500 mg/m2. Sixty-one cycles were administered to 28 women between 1989 and 1995. The median age of the patients was 58 years and median number of previous chemotherapy regimens was 2. No patient had a complete response. There was 1 partial response (PR) among 8 patients with measurable disease, and 4 PR among 20 women with evaluable disease; 2 had stable disease and 21 progressed on treatment for a response rate of 18% (95% confidence interval, 3-33%). Duration of response was 2 to 14 months, median 5 months. Survival from the start of 5-FU/leucovorin ranged from 1 to 78 months, median 5.5 months, and a mean of 10 +/- 15 months (mean +/- SD). The combination of 5-FU/leucovorin had minimal activity in this patient population. Only 2 women achieved resolution of their ascites and experienced a significant palliation.

Topics: Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; CA-125 Antigen; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Ovarian Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome

59 patients were treated for newly diagnosed metastatic ovarian germ cell tumours with POMB/ACE chemotherapy (which contains cisplatinum, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide). The median follow-up was 7.7 years. The 3 year survival is 87.8% (95% confidence interval 76.9-93.9%) and no relapses occurred more than 3 years after treatment. 4 (7%) patients had primary drug resistance to POMB/ACE and 4 (7%) have relapsed. One patient in complete remission developed secondary acute myeloid leukaemia after receiving a total of 1.3 g/m2 etoposide. 6 of 12 (50%) patients referred at relapse were salvaged by POMB/ACE. 14 of 33 (42%) women (> 18 years old) have had successful pregnancies after fertility conserving surgery and chemotherapy with no congenital abnormalities reported. The POMB/ACE regimen is as efficacious as other published regimens for ovarian germ cell tumours (OGCT) and balances a low incidence of life-threatening toxicity with a high success rate.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Child, Preschool; Cisplatin; Cyclophosphamide; Dactinomycin; Etoposide; Female; Germinoma; Humans; Leucovorin; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Remission Induction; Salvage Therapy; Survival Rate; Vincristine

Based on differential levels of membrane-associated folate binding protein (mFBP) expression, murine L1210 leukemia, human KB epidermoid carcinoma, and human IGROV1 ovarian carcinoma cells maintained under low (physiological) folate conditions (2 nM folinic acid) were used as model systems to investigate the potential role of mFBP in antifolate transport. In addition, L1210 parental cells were compared to a subline, L1210A, expressing high levels of mFBP and defective reduced folate carrier. Antifolates for which KB-derived mFBP has high affinity (5, 10-dideazatetrahydrofolic acid [DDATHF] and homo-DDATHF [0.24 and 0.78 respectively relative to folic acid]) and low affinity (methotrexate [0.002]) were chosen for this study. Protection against DDATHF/homo-DDATHF induced cytotoxicity was achieved preferentially by folic acid compared to folinic acid in IGROV1 and L1210A cells. In IGROV1 cells, cytotoxicity IC50s were increased 18- and 5.5-fold for DDATHF and homo-DDATHF respectively by 20 nM folic acid. Moreover, greater protection was observed in L1210A cells, where IC50s were increased 354- and 80-fold for these same compounds by 20 nM folic acid. Similar protection was not observed in KB cells, suggesting that KB mFBP was not functional in DDATHF transport. Although mFBP expression may be an important determinant in the cytotoxicity of antifolates for certain tumor cells, our data demonstrate a lack of correlation between levels of mFBP and function of mFBP for DDATHF transport in the models studied.

Topics: Animals; Antineoplastic Agents; Carrier Proteins; Drug Interactions; Drug Screening Assays, Antitumor; Female; Folate Receptors, GPI-Anchored; Folic Acid; Folic Acid Antagonists; Humans; KB Cells; Leucovorin; Leukemia L1210; Membrane Proteins; Mice; Ovarian Neoplasms; Receptors, Cell Surface; Tumor Cells, Cultured

The role of a membrane-associated folate binding protein (mFBP) in transport of folate analogues was investigated in three epithelial cell lines that were grown in high folate medium and folate-conditioned medium and express different levels of mFBP: human nasopharyngeal KB cells, monkey kidney MA104 cells, and IGROV-I ovarian carcinoma cells. Folate analogues were selected for which mFBP exhibits a low affinity, i.e., methotrexate (MTX) and 10-ethyl-10-deazaaminopterin (10-EdAM) or a (moderately) high affinity as compared to folic acid, i.e., N-(5[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl(-N-m ethylamino]-2-theonyl)-L-glutamic acid (ZD1694), N10-propargyl-5,8-dideazafolic acid (CB3717), and 5,10-dideazatetrahydrofolic acid. Regardless of the medium folate status, growth inhibition studies with IGROV-I and MA104 cells demonstrated a lack of correlation between the affinity of mFBP for the antifolate drugs and their sensitivity profile; both cell lines were highly sensitive to growth inhibition by MTX, 10-EdAM, ZD1694 and 5,10-dideazatetrahydrofolic acid, but were insensitive for CB3717. The same drug sensitivity profile was observed for KB cells, with the exception that these cells were also sensitive to growth inhibition by CB3717 but only in folate-conditioned medium. This overall drug sensitivity profile appeared to correlate with the differential efficiency of drug transport via the "classical" reduced folate/MTX carrier (RFC), rather than by mFBP. Characteristics that further supported functional RFC activity in KB, IGROV-I, and MA104 cells included: (a) the growth inhibitory effects of the drugs could be prevented by the reduced folate leucovorin rather than by folic acid; (b) rates for uptake of [3H]10-EdAM were 2-4-fold higher than for [3H]MTX at 1 microM extracellular concentrations and coincided with the affinity of the RFC for these drugs, rather than those of the mFBP; (c) uptake of [3H]10-EdAM and [3H]leucovorin was markedly inhibited by leucovorin and 10-EdAM, respectively, or by an N-hydroxysuccinimide ester of MTX (irreversibly labeling RFC) but only to a minor extent by folic acid or an N-hydroxysuccinimide ester of folic acid (irreversibly labeling mFBP); and, finally, (d) labeling with an N-hydroxysuccinimide ester of [3H]MTX identified a protein with a molecular weight within the range of that reported for the RFC in human leukemic cells. Altogether, these results indicate that both RFC and mFBP are coexpressed in three epithe

Topics: Aminopterin; Animals; Carrier Proteins; Cell Division; Female; Folate Receptors, GPI-Anchored; Folic Acid; Folic Acid Antagonists; Glutamates; Haplorhini; Humans; Kidney; Leucovorin; Methotrexate; Nasopharyngeal Neoplasms; Ovarian Neoplasms; Quinazolines; Receptors, Cell Surface; Tetrahydrofolates; Thiophenes; Tumor Cells, Cultured

Inhibition of clonogenic potential by the glycinamideribonucleosyl transformylase inhibitor 5,10-dideazatetrahydrofolic acid (DDATHF, Lometrexol) was evaluated in vitro in a human ovarian carcinoma cell line, SW626. Drug-induced inhibition of clonogenic potential is a function of the dose and time of exposure and is independent of the formation of DNA single-strand breaks or de novo synthesis of protein. Simultaneous treatment with 100 microM hypoxanthine completely prevented the inhibition of clonogenic potential caused by 0.5 microM DDATHF. DDATHF blocked cells in the early-middle S-phases of the cell cycle, and there was a corresponding marked reduction in the rate of DNA synthesis after drug withdrawal. The cytotoxic potential of DDATHF was modulated by the folic acid concentration present in the medium. In a medium containing 0.22 microM folic acid, DDATHF cytotoxicity was at least 100 times that in a regular medium containing 2.22 microM folic acid, levels which, however, are about 100 times those found in human plasma. DDATHF cytotoxicity differed moderately when folic acid concentrations varied between 0.22 and 0 microM, suggesting that folic acid does not necessarily antagonise DDATHF anti-tumour activity. Folinic acid at a concentration as low as 0.1 microM can completely rescue cells when given simultaneously with 0.5 microM DDATHF. When folinic acid was given 24 h after DDATHF, a reversal of cytotoxicity was observed at 0.5 and 1 microM, but to a much lesser extent than simultaneous treatment. When folinic acid was added after 48 or 72 h of DDATHF washout, even at a high concentration and for a long time, no reduction in DDATHF cytotoxicity was found. In conclusion, the study highlights the modulation of DDATHF cytotoxicity by folic acid or by folinic acid and provides further rationale for in vivo clinical investigation with these combinations.

Topics: Antineoplastic Agents; Cell Cycle; DNA, Neoplasm; Drug Screening Assays, Antitumor; Female; Folic Acid; Folic Acid Antagonists; Humans; Hypoxanthine; Hypoxanthines; Leucovorin; Ovarian Neoplasms; Tetrahydrofolates; Thymidine; Time Factors; Tumor Cells, Cultured

Twenty-nine patients with recurrent advanced stage ovarian cancer were treated with 5-fluorouracil (5-FU) and leucovorin by intravenous bolus on 5 consecutive days, repeated every 3 weeks. Twenty-one of these patients had experienced disease progression while receiving a cisplatin- or carboplatin-based regimen. There were 2 clinical complete responders and 1 partial responder to therapy (10% response rate; 95% confidence interval, 2 to 27%) and 11 individuals who experienced stable disease for periods ranging from 5 to 27 months. Of 204 cycles of therapy administered, 9 cycles were associated with hospitalization. These occurred in the more heavily pretreated members of the cohort. 5-FU and leucovorin appear to have activity in platinum-refractory ovarian cancer and form a well-tolerated regimen in most patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Drug Administration Schedule; Drug Resistance; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Platinum; Remission Induction

Twenty-five patients with advanced measurable gastric cancer were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. Fourteen patients over 65 yr old and/or with a poor general status received first-line treatment, and eleven younger patients second-line. The response rate was 43.5% in 23 evaluable patients. There were 2 complete responses (8.7%) and 8 partial responses (34.8%). Median survival was 6 months in first-line and 8 months, calculated from start of folinic acid-5FU, in second-line. Toxicity was mild without WHO Grade greater than 2 events. This combination is effective for advanced gastric cancer in poor-prognosis patients and requires further studies.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms

Administration i.p. of 10-ethyl-10-deazaaminopterin (10EDAM) with cis-diamminedichloroplatinum(II) (cis-Pt) had significant antitumor activity against the murine ovarian tumor. This tumor is a teratoma originating in the ovary with pathogenesis and metastatic properties similar to those of human ovarian cancer. Drug was given on a schedule of once every 3 days for 3 doses 1 or 2 days after i.p. implant of 10(7) tumor cells. Despite the 2-fold attenuation of dosage required, antitumor activity of the combination (increased life span, 161%) was approximately twice that obtained with maximum tolerated doses of either agent alone and tumor-free, long-term survivors were obtained. Incorporation of s.c. calcium leucovorin administration 16 h after each dose of 10EDAM and cis-Pt allowed a 4-fold increase in dosage of 10-EDAM without an increase in toxicity, increased median survival by an additional 120%, and quadrupled the number of tumor-free, long-term survivors to 40% of treated animals. By comparison, methotrexate was only modestly active against this tumor model either as a single agent, with cis-Pt, or with delayed s.c. calcium leucovorin administration. These results appear to suggest that 10EDAM with cis-Pt may have considerable potential for intracavitary therapy of human cancer, including ovarian carcinoma, particularly when incorporating delayed systemic calcium leucovorin administration.

Topics: Aminopterin; Animals; Cisplatin; Drug Evaluation, Preclinical; Female; Folic Acid Antagonists; Injections, Intraperitoneal; Injections, Subcutaneous; Leucovorin; Male; Methotrexate; Mice; Mice, Inbred C3H; Ovarian Neoplasms

In this study, A2780 human ovarian carcinoma cells were grown in folinic acid in contrast to folic acid, and the molecular and biochemical properties of cisplatin-resistant A2780 cells were analyzed for changes in the dTMP synthase cycle. At concentrations of folinic acid that were optimal for cell growth (10(-8) M), the ED50 for cisplatin was 2.5 and 43 microM in the A2780S and A2780DDP cells, respectively. Resistance to cisplatin was associated with a 2-fold cross-resistance to 5-fluorodeoxyuridine and 5-fluorouracil as well as a 3-fold increase in both dTMP synthase activity and mRNA. The ED50 for methotrexate was similar in both A2780S and A2780DDP cells (1.2 microM). When both the A2780S and A2780DDP cells were grown in folinic acid, there was no significant difference in the level of dihydrofolate reductase activity. This data would suggest that cisplatin resistance is associated with changes in folate metabolism.

Topics: Cell Line; Cisplatin; DNA, Neoplasm; Drug Resistance; Female; Humans; Kinetics; Leucovorin; Ovarian Neoplasms; RNA, Neoplasm; Tetrahydrofolate Dehydrogenase; Thymidylate Synthase; Transcription, Genetic

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Female; Floxuridine; Fluorouracil; Humans; Iliac Artery; Infusions, Intra-Arterial; Leucovorin; Male; Melanoma; Methotrexate; Middle Aged; Ovarian Neoplasms; Pelvic Neoplasms; Prostatic Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms

Methotrexate (MTX) (1--7.6 g/m2) with leucovorin rescue was given to 19 women with stage III-IV ovarian carcinoma after induction of remission with surgical treatment and chemotherapy or after relapse. Adequate hydration with alkalinization prevented nephrotoxicity and no cumulative myelosuppression was observed. Serum MTX levels in nontoxic patients averaged 1 X 10(-6) M 24 hours following a 30-minute iv infusion of MTX at 3 g/m2. Among nontoxic women there was a 50-fold difference in the MTX level which correlated with the mean serum creatinine level. Response was assessed after 6--12 weeks of treatment by laparoscopy in patients with nonpalpable intra-abdominal tumor implants or by physical examination in patients with palpable masses. Despite the high levels of MTX achieved with the weekly schedule, only one partial response occurred among eight patients with visible or palpable metastatic lesions. Progressive disease was observed after 6--12 weeks of treatment in four of eleven women who began to receive MTX without evidence of disease or with lesions of less than 1.5 cm in diameter. MTX at the dose and schedule used in the present study appears to be of no benefit in the treatment of advanced ovarian cancer.

Topics: Adult; Aged; Bone Marrow; Creatinine; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Kidney; Leucovorin; Methotrexate; Middle Aged; Ovarian Neoplasms

Topics: Adenocarcinoma; Alkylating Agents; Antineoplastic Agents; Bone Marrow; Cisplatin; Cyclophosphamide; Drug Resistance; Drug Therapy, Combination; Female; Humans; Kidney; Leucovorin; Methotrexate; Ovarian Neoplasms; Recurrence

The authors have analysed the influence exercised by the combined therapy of the ovary carcinoma on the plasma ribonuclease activity in Wistar rats. The medicaments "Proresid", "VM-26", and "Methotrexat" together with a percutaneous irradiation of the abdomen did not alterate perceptibly the enzyme activity during the experiment, but there was a considerable reduction of the enzyme activity after an application of "Endoxan", "Adriblastin" and "Methotrexat" with subsequent administration of "Leukovorin". The most violent ribonuclease suppression, however, was obtained by an intraperitoneal instillation of radiogold and a fractioned percutaneous irradiation of the abdomen with intercalated administration of "Endoxan".

Topics: Animals; Cyclophosphamide; Doxorubicin; Female; Leucovorin; Methotrexate; Ovarian Neoplasms; Podophyllin; Podophyllotoxin; Rats; Ribonucleases

Experience with chemotherapy in advanced gynecologic malignancies is limited. In 6 patients, 2 of 4 with carcinoma of the cervix, and 1 patient with carcinoma of the ovary achieved partial remission when treated with a regimen of high dose methotrexate (240 mg/m2) followed by leucovorin rescue. On patient with metastatic trophoblastic disease achieved complete response (greater than 24 months). The number of doses of leucovorin 'rescue' was based on creatinine clearance. The advantage of rapid response and moderate toxicity indicate the need for further study of this regimen in the treatment of gynecologic malignancies.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Leucovorin; Methotrexate; Middle Aged; Ovarian Neoplasms; Pregnancy; Trophoblastic Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Adolescent; Age Factors; Aspartate Aminotransferases; Child; Child, Preschool; Female; Half-Life; Hematopoiesis; Humans; Kidney; Leucovorin; Liposarcoma; Methotrexate; Neoplasm Metastasis; Neoplasms; Osteosarcoma; Ovarian Neoplasms; Rhabdomyosarcoma; Sarcoma, Ewing; Teratoma

Topics: Age Factors; Child; Choriocarcinoma; Female; Humans; Leucovorin; Methotrexate; Neoplasm Metastasis; Ovarian Neoplasms; Pregnancy; Prognosis

Topics: Breast Neoplasms; Choriocarcinoma; Female; Head; Head and Neck Neoplasms; Humans; Leucovorin; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Methotrexate; Neoplasm Metastasis; Neoplasms; Ovarian Neoplasms; Pregnancy; Remission, Spontaneous; Uterine Cervical Neoplasms