levoleucovorin and Uterine-Cervical-Neoplasms

The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonrandomized, phase 2 Yale University cisplatin, bleomycin, methotrexate, and 5-FU protocol are presented.. Sixty-seven patients were prospectively accrued with a median follow-up of 5.4 years, and standard parameters of toxicity and efficacy were studied. Both univariate and multivariate analyses were applied.. The 5-year disease-free survival of 78% for the 25 patients in the adjuvant group, of which 80% had high-risk features including positive margins, parametria, and lymph nodes and 28% had adenocarcinomas, was comparable to recent relevant literature. Only 64% of patients in this group received consolidation radiation therapy, which did not impact on survival. Only 12% of patients recurred distantly. Notably, those who received 4 months or more of chemotherapy had prolonged survival (P = 0.012). In the neoadjuvant group, chemotherapy response rate among 42 patients (with stages 1B-IIIB cancer) was 79% (50% partial response, 29% complete response), and no patient progressed. In the subgroup of 22 patients who underwent surgery after chemotherapy, 59% had nonsquamous histology. Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy. Ninety-five percent received postoperative radiation therapy. There was a 9% pathologic complete response rate, with positive lymph nodes found in 27%. Notably, those who received 3 months or less of chemotherapy had improved overall survival (P = 0.030). Survival rates of these 22 patients at 3 and 5 years were 73% and 63%, respectively. Although not randomized, these survival rates were similar to those achieved with chemoradiation.. Although there are several logistical/design features of the cisplatin, bleomycin, methotrexate, and 5-FU regimen that are not in line with the current chemotherapy era, our experience with this well-tolerated regimen can serve as a proof of principle. Our data suggests that both neoadjuvant and adjuvant cisplatin-based neoadjuvant chemotherapy may have their place. It also raises the possibility that the optimal duration of chemotherapy in adjuvant cases should be longer than in neoadjuvant cases.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Maximum Tolerated Dose; Methotrexate; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prospective Studies; Survival Rate; Treatment Outcome; Uterine Cervical Neoplasms; Young Adult

The objective of this study is to assess tumour response to neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer using magnetic resonance (MR) to monitor tumour volume and changes in molecular profile and to compare the survival to that of a control group. Eligibility included Stage Ib-IIb previously untreated cervical tumours >10 cm(3). Neoadjuvant chemotherapy in 22 patients (methotrexate 300 mg x m(-2) (with folinic acid rescue), bleomycin 30 mg x m(-2), cisplatin 60 mg m(-2)) was repeated twice weekly for three courses and followed by radical hysterectomy. Post-operative radiotherapy was given in 14 cases. A total of 23 patients treated either with radical surgery or chemoradiotherapy over the same time period comprised the nonrandomised control group. MR scans before and after neoadjuvant chemotherapy and in the control group documented tumour volume on imaging and metabolites on in vivo spectroscopy. Changes were compared using a paired t-test. Survival was calculated using the Kaplan-Meier method. There were no significant differences between the neoadjuvant chemotherapy and control groups in age (mean, s.d. 43.3+/-10, 44.7+/-8.5 years, respectively, P=0.63) or tumour volume (medians, quartiles 35.8, 17.8, 57.7 cm(3) vs 23.0, 15.0, 37.0 cm(3), respectively, P=0.068). The reduction in tumour volume post-chemotherapy (median, quartiles 7.5, 3.0, 19.0 cm(3)) was significant (P=0.002). The reduction in -CH(2) triglyceride approached significance (P=0.05), but other metabolites were unchanged. The 3-year survival in the chemotherapy group (49.1%) was not significantly different from the control group (46%, P=0.94). There is a significant reduction in tumour volume and -CH(2) triglyceride levels after neoadjuvant chemotherapy, but there is no survival advantage.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Female; Humans; Hysterectomy; Leucovorin; Magnetic Resonance Imaging; Methotrexate; Middle Aged; Neoadjuvant Therapy; Radiotherapy, Adjuvant; Survival Analysis; Treatment Outcome; Uterine Cervical Neoplasms

The objective of the study was to determine the response rate and associated toxicity of 5-fluorouracil and high-dose leucovorin in patients with recurrent adenocarcinoma of the cervix.. Between December 1993 and October 1995, 53 patients with recurrent adenocarcinoma of the cervix were entered into a Phase II trial utilizing 200 mg/m2 of intravenous (iv) leucovorin with 370 mg/m2 of i.v. 5-fluorouracil daily for 5 days every 4 weeks for two courses, then every 5 weeks until disease progression. Eligibility criteria were a Gynecologic Oncology Group (GOG) performance status of 0-2, adequate bone marrow reserve, adequate liver function with bilirubin < or = 1.5 x normal and SGOT and alkaline phosphatase < or = 3 x normal, serum creatinine < or = 2 mg%, and signed informed consent. Standard GOG toxicity and response criteria were employed.. Six patients were ineligible because of wrong cell type (N = 3), insufficient pathology materials (N = 2), or a second primary (N = 1); therefore 45 were evaluable for toxicity. Two patients did not have adequate response assessment; thus, 43 were evaluable for response. The median age was 50 (range, 28-79). Prior chemotherapy had been administered to 16 patients and radiotherapy to 40 patients. The median number of courses delivered was three (range, 1-22). The site of evaluable disease was pelvic in 25 patients and extra-pelvic in 18. Grade 3 neutropenia was seen in 17.8% (8/45) patients and 35.5% (16/45) developed grade 4 neutropenia. Grade 3 or 4 thrombocytopenia was seen in 1 patient each (2.1%). Grade 3 gastrointestinal toxicity with nausea, vomiting, diarrhea, dehydration, or stomatitis was of grade 3 severity in 11.1% (5/45) and grade 4 in 6.7% (3/45). There were four partial responses and two complete responses for an overall response rate of 14%. The duration of the complete responses was 17.3 and 8.8+ months. None of the patients with responses had previously received chemotherapy.. The schedule of 5-fluorouracil and leucovorin exhibits moderate activity in patients with previously treated adenocarcinoma of the cervix and should be considered for a trial in chemotherapy-naive patients.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Neoplasm Recurrence, Local; Treatment Outcome; Uterine Cervical Neoplasms

The addition of leucovorin to 5-fluorouracil (5-FU) has been shown to improve the response rate in recurrent colon cancer. The combination of low-dose leucovorin and 5-FU was previously tested by the Gynecologic Oncology Group (GOG) and did not produce response rates greater than rates using 5-FU alone. From June 1990 to April 1992, 55 patients with unresectable recurrent squamous cervical cancer received high-dose leucovorin at 200 mg/m2 i.v. bolus, followed by 5-FU at 370 mg/m2 i.v. bolus daily for 5 days every 4 weeks for the first two courses. Subsequent courses were given every 5 weeks. The median number of courses delivered was two (range 1-15). Fifty patients were evaluable for toxicity and 45 for response. Prior radiotherapy had been given to 43 patients and prior chemotherapy to 38. The overall response rate was 8.8% (95% confidence interval, 2.5-21.2%). There were two complete responses (4.4%) and two partial responses (4.4%). One response was in the pelvis and three were outside the pelvis. None of the extrapelvic responses had received irradiation at the site of measurable disease. The major adverse effect was granulocytopenia, with 15/50 (30%) experiencing GOG grade 3 or 4 granulocytopenia. The median white blood count for patients experiencing leukopenia was 2,000 (range 400-3,800). Grade 3 or 4 gastrointestinal toxicity was seen in 12 patients (24%). In this pretreated population, patients receiving high-dose leucovorin with 5-FU had moderate toxicity but only minimal activity.

Topics: Antidotes; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Female; Fluorouracil; Humans; Leucovorin; Neoplasm Recurrence, Local; Uterine Cervical Neoplasms

Thirty patients with recurrent squamous cell carcinoma of cervix uteri no longer amenable to control with surgery and/or radiotherapy were treated with a combination of ifosfamide, 5-fluorouracil, and Leucovorin every 4 weeks. The response rate was 53% (complete response, 33%; partial response, 20%). Response rates outside and inside irradiated area were 68 and 27%, respectively. The median progression-free interval was 7 months, and the median overall survival was 12 months. Adverse effects included primarily leukopenia, and dose reduction was necessary in 18 patients (60%). The present combination is active in the treatment of recurrent cervical cancer with a high response rate. The long-term survival is however still unsatisfactory.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Female; Fluorouracil; Humans; Ifosfamide; Leucovorin; Middle Aged; Neoplasm Recurrence, Local; Survival Analysis; Uterine Cervical Neoplasms

Twenty-eight patients with recurrent squamous carcinoma of the cervix not amenable to cure by further surgery or radiation therapy were entered into a Phase II trial utilizing i.v. leucovorin 20 mg/m2 followed by 5-fluorouracil 425 mg/m2 administered daily for 5 days every 4 weeks for the first two courses and then every 5 weeks. One patient never received therapy, and three are inevaluable for response; therefore, 27 patients were evaluable for toxicity and 24 for response. Twenty-three patients had received prior radiotherapy, and 16 had received prior chemotherapy. There was one partial response 4.2% (95% confidence intervals for a response of 0 to 21%). Although toxicity was acceptable with 11 of 27 (41%) grade 3 or 4 leukopenia, 1 of 27 (4%) grade 3 thrombocytopenia, and 3 of 27 (11%) grade 3 or 4 gastrointestinal toxicity, this dose schedule of 5-fluorouracil and leucovorin has minimal activity in recurrent squamous carcinoma of the cervix.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Recurrence; Uterine Cervical Neoplasms

Non-Hodgkin's Lymphomas (NHL) frequently affect the uterine corpus, cervix, and vagina in cases of advanced disease. However, these organs are rarely the site of origin of this type of neoplasia. Because of the rarity of primary genital tract lymphomas, a standard treatment has not been defined.. Three patients with large B-cell primary Non-Hodgkin's lymphoma of the lower genital tract (vaginal, cervical and cervico-vaginal) presented with bulky lesions and underwent diagnostic evaluation, staging, and chemotherapy with adriamycin-containing regimens. All three patients, including two with stage IIE and one with stage IE disease demonstrated complete remission and are alive and well without evidence of disease at 10, 7, and 6 years of follow-up, respectively.. Our observations suggest that young patients with large B-cell lymphomas of lower genital tract stages I-IIE, even with bulky lesions, may benefit from chemotherapy alone as initial treatment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Methotrexate; Neoplasm Staging; Prednisone; Uterine Cervical Neoplasms; Uterine Neoplasms; Vaginal Neoplasms; Vincristine

Primary extranodal lymphomas of the genital tract are rare.. As there is no current consensus in its management, we present two further cases and their treatment with neoadjuvant chemotherapy, followed by radiation therapy. A radical hysterectomy with bilateral pelvic lymphadenectomy was performed after primary treatment in one case. Clinical response was complete in both cases and pathological response was documented in one.. Complete response of these lymphoid neoplasms can be achieved by neoadjuvant chemotherapy followed by external irradiation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Methotrexate; Neoadjuvant Therapy; Prednisone; Uterine Cervical Neoplasms; Vincristine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin, beta Subunit, Human; Diagnosis, Differential; Female; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Parity; Pregnancy; Ultrasonography, Prenatal; Uterine Cervical Neoplasms

Chemotherapy for cervical cancer patients with recurrent and/or advanced disease has been complicated by excessive toxicity and short duration of responses, leading to little or no improvement in survival. Modification of drug scheduling and delivery of platinum, bleomycin, methotrexate, and 5-FU has resulted in a new combination regimen with little toxicity and a survival advantage for responders. PBM (platinum 80 mg/m2 D1, bleomycin 10 mu/m2/day D3-6, methotrexate 150 mg/m2 D15, 22 with leucovorin) is alternated with PFU (platinum 100 mg/m2 D1, 5-FU 1000 mg/m2/day D2-5) q 4 weeks for 3-6 months. The platinum, bleomycin, and 5-FU were delivered by continuous infusion. Twenty-three patients with recurrent and 17 with advanced cervical cancer are evaluable; 91% of patients with recurrent disease had received prior radiation therapy. The response rate was 30.4% in those with recurrent disease, and 41.2% in those with advanced disease, with 86 and 42.9% of responders respectively achieving a CR. Survival data were analyzed for each group separately, as well as for the combined recurrent/advanced disease group (N = 40). The results and significance were not changed by the groupings. In the combined recurrent/advanced group, median duration of response was 10.5 months, mean 20.1, and the median overall survival was 11 months, mean 20.5 +/- 3.5. There was a survival advantage accrued to the responders (median, 28 months) vs the nonresponders (10 months) (P = 0.0005 by log rank test). Moreover, there was a significant difference in progression-free interval between responders vs nonresponders (P = 0.0001), as well as between responders and those with stable disease (P = 0.001). This regimen was very well tolerated and there was no significant pulmonary toxicity. Furthermore, in the subset of 23 patients who had recurrent disease, 67% achieved palliation of pain. Experience with this protocol supports the continuing use of chemotherapy in the management of cervical cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma; Cisplatin; Female; Fluorouracil; Humans; Leucovorin; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Survival Analysis; Treatment Outcome; Uterine Cervical Neoplasms

Three patients with small-cell carcinoma of the cervix entered a pilot study of combination chemotherapy with agents that are not cross-resistant. Two patients had local disease and the third had extensive metastatic disease of the liver. The regimen consisted of weekly chemotherapy for 16 weeks with cisplatin, vincristine, methotrexate, doxorubicin, cyclophosphamide and etoposide followed by radiotherapy and/or surgery. The two patients with local disease achieved a pathological complete response, with no evidence of disease at 24 months and 15 months from diagnosis. The third patient achieved a partial response and is alive at 13 months with progressive disease. Side-effects were tolerable.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Pilot Projects; Prednisone; Uterine Cervical Neoplasms; Vincristine

Primary cervical choriocarcinoma is a rare disease; since 1915 only about 60 cases have been published. The case presented here can be defined as primary cervical choriocarcinoma since it fulfills all the criteria delineated previously.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cervix Uteri; Choriocarcinoma; Female; Humans; Immunoenzyme Techniques; Leucovorin; Methotrexate; Uterine Cervical Neoplasms

A 22-year-old nulligravida presented with a stage IE/IIIB primary malignant lymphoma of the cervix which measured 8 cm in diameter. In order to preserve reproductive potential, a 12-week course of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin was administered. One month later a 4-cm-diameter left parametrial mass was excised at laparotomy; no tumor was detected in the specimens obtained. Menses resumed after an additional 6 months. The patient was clinically disease-free at the 33-month follow-up.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma; Methotrexate; Prednisone; Uterine Cervical Neoplasms; Vincristine

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Time Factors; Uterine Cervical Neoplasms

Fourteen patients with advanced or locally recurrent squamous cell carcinoma of the uterine cervix were treated with bleomycin, vincristine, and moderately high dose methotrexate with citrovorum rescue. Two patients (14%) had a partial response; no patient had a complete response. Two patients were felt to have significant bleomycin associated pulmonary toxicity. This chemotherapy regimen is not felt to be clinically useful in our patient population.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Female; Humans; Leucovorin; Lung Diseases; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Uterine Cervical Neoplasms; Vincristine

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

The results of treating 59 patients with advanced carcinoma of the cervix with Adriamycin and methotrexate are given. Five combinations of the two cytotoxic drugs have been evaluated, differing only with regard to the methotrexate. One particular regimen has been shown to be effective with a relatively high remission rate coupled with a low rate of side effects.

Topics: Alopecia; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Humans; Leucovorin; Leukopenia; Methotrexate; Mouth Diseases; Remission, Spontaneous; Taste Disorders; Ulcer; Uterine Cervical Neoplasms

Fourteen patients with advanced localized gynecologic cancer were treated with 44 courses of intraarterial pelvic infusion chemotherapy. All patients received methotrexate with folinic acid rescue; 9 patients also received vincristine. Tumor regression was observed in 3 of 14 patients (21.4%). In 5 patients there were major complications related to 28 intraarterial catheter placements. Two patients developed leukopenia following chemotherapy. The value of intraarterial infusion chemotherapy in gynecologic cancer is limited. Its use in gynecologic oncology is discussed.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Catheterization; Female; Genital Neoplasms, Female; Humans; Infusions, Intra-Arterial; Leucovorin; Methotrexate; Middle Aged; Pelvis; Uterine Cervical Neoplasms; Vincristine

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: 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

Topics: Carcinoma; Female; Humans; Injections, Intramuscular; Leucovorin; Methotrexate; Uterine Cervical Neoplasms

Topics: Carcinoma; Female; Folic Acid; Folic Acid Antagonists; Humans; Leucovorin; Methotrexate; Uterine Cervical Neoplasms

Topics: Carcinoma; Female; Folic Acid; Folic Acid Antagonists; Humans; Injections, Intramuscular; Leucovorin; Methotrexate; Uterine Cervical Neoplasms