levoleucovorin and Carcinoma--Small-Cell

Topics: Antineoplastic Agents; Bone Marrow; Bone Marrow Transplantation; Carcinoma, Small Cell; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Recurrence; Remission, Spontaneous; Research Design; Time Factors; Transplantation, Autologous

Topics: Adult; Alkylating Agents; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Child; Cyclophosphamide; Doxorubicin; Drug Combinations; Drug Therapy, Combination; Female; Fluorouracil; Humans; Immunotherapy; Leucovorin; Male; Melphalan; Methotrexate; Neoplasm Metastasis; Neoplasms; Osteosarcoma; Prednisone; Rhabdomyosarcoma; Testicular Neoplasms; Thiotepa; Vinblastine; Vincristine

Ifosfamide-based chemotherapy has already been the basis of three separate clinical trials. In this study, ifosfamide was administered to lung cancer patients who had failed to respond to previous chemotherapy, to assess its response rate and toxicity.. From January 1993 to December 1996, 21 patients were treated, including eight patients with small cell lung cancer (SCLC) and 13 with non-small cell lung cancer (NSCLC). Patients who had histocytologically confirmed lung cancer, were previously treated with chemotherapy, had a measurable lesion(s), were younger than 75 years of age, had an Eastern Cooperative Oncology Group performance status of 0-3 and adequate marrow, renal and liver function were eligible for inclusion in this study. For SCLC patients, ifosfamide 2.4 g/m2 intravenous (i.v.) infusion was given over 30 minutes on days 1-3 every four weeks. For NSCLC two regimens were used: IFL (ifosfamide 2 g/m2, 5-fluorouracil (FU) 600 mg/m2 and leucovorin 50 mg/m2 i.v. infusion on days 1-3 every four weeks) and LIFE (leucovorin 50 mg/m2, ifosfamide 1 g/m2, 5-FU 400 mg/m2 and epirubicin 12 mg/m2 i.v. infusion on days 1-3 every four weeks). For NSCLC patients, IFL was used for the first two years of treatment and LIFE was used in the last two treatment years. All patients were evaluated for treatment response and toxicity.. The major toxic effect, myelosuppression (grade 3 or 4 leukopenia), occurred in 62.5% of SCLC patients and 23.1% of NSCLC patients during treatment, and in 62.5% and 10% of SCLC and NSCLC patients, respectively, throughout the course. Only one SCLC and one NSCLC patient experienced febrile neutropenia. One toxic death, attributed to febrile neutropenia, was documented in a patient with SCLC. Alopecia was ubiquitous. Other toxicities were uncommon and mild. The overall response rate was 50% in SCLC and 7.7% in NSCLC. The median time to disease progression was 61 days in SCLC and 47 days in NSCLC. Median survival was 172 days in SCLC and 173 days in NSCLC.. The study results suggest that ifosfamide chemotherapy is active with an acceptable toxicity profile in previously treated SCLC patients. However, it lacks efficacy in NSCLC patients who have been previously treated.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Epirubicin; Female; Fluorouracil; Humans; Ifosfamide; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Salvage Therapy

Fourteen patients with small cell lung cancer (SCLC) previously treated with one or two chemotherapy regimens were entered in this study. 5-Fluorouracil 370 mg/m2 or 300 mg/m2 was given with folinic acid 200 mg/m2 by i.v. rapid infusion on days 1 through 5. Cycles were repeated every 28 days. There were no objective responses. One patient had stable disease for 47 weeks. The overall median survival duration was 23 weeks. Toxicity was comparable to that seen in other studies of 5-fluorouracil plus folinic acid.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Survival Rate

Fifty-three patients with small cell carcinoma of the lung were treated with chemotherapy and radiotherapy, 40 Gy in the chest tumour. Intrathoracic failure occurred in 89% of the cases with extensive disease and in 60% of those with limited disease. Since 86% of all failures were localized within the target volume, one can conclude that in most cases the radiation dose was too low for eradication of the tumour. The treatment technique resulted in dose inhomogeneities of more than +/- 5% in 45% of the cases. The high local failure rate might indicate the need of improved radiotherapy, in the first place higher radiation dose. However, 82% of the patients with limited disease and local failure and 50% of those without local failure also developed distant metastases. This might indicate that the curative potential of improved thoracic radiotherapy probably is limited. Besides, lethal treatment toxicity affected particularly patients in whom local cure had been achieved, indicating the difficulty of increasing the treatment intensity without increasing the lethal toxicity in potentially curable cases.

Topics: Adult; Aged; Carcinoma, Small Cell; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Radiotherapy Dosage; Survival Analysis; Vincristine

Eight patients with local Stage II (T2N1) and III (T3N0, T3N1, T2N2) small cell lung cancer received combination chemotherapy prior to elective surgery to assess the effectiveness of such a regimen in improving operability, preventing local relapse and extending survival. The regimen was well tolerated and prevented local relapse. However, the median time to recurrence of disease was 10 months and the median survival time 13 months, results which are similar to those achieved with chemotherapy and radiotherapy. Distant metastases, particularly in the brain, occurred predictably indicating that successful adjuvant surgery, despite preventing local relapse, may not afford additional survival benefit with currently available drug regimens.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Lung Neoplasms; Lymphatic Metastasis; Male; Methotrexate; Middle Aged; Neoplasm Staging; Pneumonectomy; Preoperative Care; Remission Induction; Vincristine

In order to determine whether combination chemotherapy offered any advantage over single-agent therapy in cases of metastatic non-small cell bronchogenic carcinoma, we performed a randomized study in 56 patients comparing combination chemotherapy (cyclophosphamide, doxorubicin, methotrexate, procarbazine, leucovorin--CAMP-L) with a regimen in which the same drugs were given sequentially (methotrexate/leucovorin followed by cyclophosphamide/doxorubicin at progression). Of the patients receiving the combination, 52% (14 of 27) had either a partial response or stable disease, compared to 17% (5 of 29) in the sequential group. Of the patients with adenocarcinoma, those in the combination group had a significantly longer survival than those treated in the sequential group (medians, 10.0 vs 2.8 months; P less than 0.01); such a difference could not be demonstrated for patients with squamous carcinoma. Patients who achieved a partial response had a median survival of 15.3 months; those with stable disease survived a median of 10.0 months; and those with no response survived a median of 2.5 months (P less than 0.0001). Four patients died from chemotherapy-related complications: three from methotrexate toxicity and resultant infection and one from pneumonia associated with neutropenia. We conclude that the short survival of non-responding patients and the survival benefit accompanying response or stabilization make early aggressive combination therapy useful for patients with metastatic non-small cell lung cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Clinical Trials as Topic; Cyclic AMP; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Procarbazine

Since 1974, 120 previously untreated patients with small cell carcinoma of the lung seen in Therapeutic Radiology at The Medical College of Wisconsin have been entered into one of 4 successive studies. Study I used thoracic irradiation (TI) alone (4500-6000 rad in 3-6 weeks) with chemotherapy at progression. Study II randomized patients with limited disease to TI (3000 rad in 2 weeks) plus either cyclophosphamide, doxorubicin, vincristine (CAV) or total body irradiation (TBI); patients with extensive disease received TI + CAV. Study III employed prophylactic cranial irradiation (PCI) plus CAV and withheld TI unless there was incomplete response or recurrence. Of 93 evaluable patients from the first three studies, 55 had limited and 38 extensive disease. Study I (37 patients) showed a 62% complete response (CR) rate; 43% failed in the chest, 14% had brain metastases, and the median survival was only 22 weeks in spite of a preponderance of limited disease patients. Study II (27 patients) showed a CR of 59%; 30% had brain metastases and the median survival was 48 weeks. Study II patients (29) had a 69% rate; 72% failed in the chest, 4% with PCI developed brain metastases, and the median survival was 50 weeks. In March, 1979, Study IV was initiated; patients receive PCI (2500 rad in 2 weeks) plus high dose CAV, methotrexate and leucovorin. After 6 cycles, consolidation TI (3750 rad in 3 weeks) is given to patients with complete response. Preliminary results with 27 patients treated on this study show a 67% CR rate, a 41% chest failure rate (but only 11% for the patients who received thoracic irradiation) and no intracranial failures, but a 13% extracranial CNS failure rate. PCI, TI and spinal irradiation may be necessary to maximize the probability of long term disease free survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Radiotherapy Dosage; Vincristine; Whole-Body Irradiation

A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR and high-dose MTX with citrovorum rescue) and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also rendomized: 1) to determine the effects of prophylactic whole brain irradiation; and 2) to establish the effects of maintenance chemotherapy. Survival, frequency of response and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (40% vs. 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs. 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic while brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival.

Topics: Antineoplastic Agents; Brain Neoplasms; Carcinoma, Small Cell; Clinical Trials as Topic; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Random Allocation; Remission, Spontaneous; Time Factors; Vincristine

Topics: Antineoplastic Agents; Bone Marrow; Bone Marrow Transplantation; Carcinoma, Small Cell; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Recurrence; Remission, Spontaneous; Research Design; Time Factors; Transplantation, Autologous

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Brain Neoplasms; Breast Neoplasms; Camptothecin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Chemotherapy, Adjuvant; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Mass Screening; Medical Oncology; Neoplasms; Organoplatinum Compounds; Societies, Medical

Topics: Adenocarcinoma; Aged; Carcinoma, Small Cell; Female; Humans; Intestinal Neoplasms; Leucovorin; Lung Neoplasms

An intensive weekly chemotherapeutic treatment for extensive disease small-cell lung cancer was piloted in 14 patients. The regimen consisted of 6 drugs. Two drugs were given each week for a total of 12 weeks of treatment. Modifications were required in the protocol to attempt to overcome excessive toxicity. Unexpected toxicity included anemia requiring transfusions in 8 of 10 patients completing treatment, sepsis in 8 of 14 with 3 related deaths, and prolonged grade III motor neurotoxicity in 2 patients. All 3 patients who died of sepsis had shown evidence of response, and 8 of the remaining 11 had 90% or greater tumor shrinkage. Two others had a partial response. Median survival time for all patients was 9.3 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Pilot Projects; Recurrence; Treatment Outcome; Vincristine

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

Eighty-two patients with small cell lung cancer (SCLC), 32 with limited disease, were treated with alternating chemotherapy. Eight courses were administered at weekly intervals, and responding patients received radiotherapy to sites of bulk disease. Overall response rate was 76.8%. Overall median survival was 265 days, 408 days in patients with limited disease. The median symptom free period after chemotherapy was completed was 123 days. These results are comparable with those in reports of chemotherapy of longer duration and warrant the further investigation of short duration treatment in this disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Time Factors; Vincristine

The study of stem cell defects in man after cytoreductive therapy appears to be of particular importance since hematotoxicity represents the major limiting side effect in many instances. On the other hand, such studies are met by difficult methodological problems. In particular, bone marrow sampling in man cannot be done on a quantitative basis. Furthermore, ethical considerations restrict the sampling of serial bone marrow specimens. We have studied the reaction of hematopoiesis including stem cells in man with the available methods, in particular CFU-GM (CFU-C), CFU-E, and BFU-E in bone marrow (BM) and peripheral blood (PB) during the course of various cytostatic regimens given for adjuvant and palliative chemotherapy of human cancer. Major findings of these studies were The acute reaction of BM stem cells and differentiated BM precursor pools corresponds to the mechanisms known to be effective in animal experiments. The PB CFU-GM may be of particular importance in man in demonstrating long-term derangements. In an attempt at quantification of human BM data, an index was developed from BM spicule morphometry and from standardized BM aspirate cellularity. Stem cell defects in BM and PB were observed that did not show up in the PB counts, in particular after nitrosoureas. Indication of prolonged derangements in stem cells up to five years after chemotherapy were observed after adjuvant therapy for breast cancer. From these data, it appears advisable to study stem cell data in man for newly developed chemotherapeutic regimens in order to minimize early and late side effects on hematopoiesis.

Topics: Animals; Antineoplastic Agents; Blood Cells; Bone Marrow; Breast Neoplasms; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Fluorouracil; Gastrointestinal Neoplasms; Hematopoietic Stem Cells; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Nitrosourea Compounds; Regeneration; Reticulocytes; Vincristine

Most cancerocidal agents have myelosuppression as their major toxicity. In some clinical studies it has been possible to show a relationship between the amount of administered drug and the therapeutic efficacy. Within any defined protocol, however, there may be much variability in the severity of myelosuppression. We attempted to determine whether the tumor response might be related to this toxicity. We evaluated a total of 177 patients with small cell bronchogenic carcinoma, treated by five successive regimens of combination chemotherapy, consisting of either cyclophosphamide and vincristine alone or with doxorubicin or doxorubicin plus bacillus Calmette-Guerin (BCG) or doxorubicin plus methotrexate, for a number of prognostic factors (age, sex, extent of disease, performance status, sites and number of metastases, serum LDH and alkaline phosphatase, weight loss, leukopenia, and thrombopenia). Leukopenia (mean 415 +/- 478/mm3, range 0-2000/mm3) had a weak influence on the incidence of complete remission, which was highest with the least severe nadir (P = 0.027). Thrombopenia was a nonsignificant factor (P = 0.738). Both leukopenia and thrombocytopenia had no influence on the overall survival. Because these drug combinations were based on cyclophosphamide, which requires metabolic activation, we evaluated the relationship of myelosuppression and the incidence of response in a second group of patients with small cell bronchogenic carcinoma treated with a VP16, cyclophosphamide, doxorubicin, vincristine sulfate protocol. In this analysis, no relationship could be detected between remission and myelosuppression. Granulocytopenia or thrombocytopenia also-showed no significant influence on the achievement of long-term survival beyond 36 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Bronchogenic; Carcinoma, Small Cell; Cyclophosphamide; Dactinomycin; Doxorubicin; Etoposide; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Vincristine

Few studies have incorporated high-dose methotrexate (MTX) with leucovorin rescue in the treatment of small cell lung cancer (SCLC). Potentially therapeutic levels of MTX can be achieved in the central nervous system (CNS) by systemic administration of high doses of this drug. Utilizing a combination chemotherapy program of Adriamycin, vincristine, cyclophosphamide, and methotrexate, 31 patients were sequentially assigned to receive either low-dose MTX (40 mg/m2), or high-dose MTX (500 mg/m2) with leucovorin rescue. Radiation therapy to the primary site was also administered. At these dosage levels there were no statistically significant differences in response rate or survival between the two groups. High-dose MTX did not prevent the appearance of CNS disease; there being 2/15 and 3/15 CNS relapses in the HD MTX and LD MTX treated groups, respectively. The occurrence of CNS disease did not significantly affect overall survival as compared to patients not similarly affected.

Topics: Aged; Carcinoma, Small Cell; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukopenia; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Nervous System Neoplasms; Paraneoplastic Syndromes; Smoking; Thrombocytopenia

Ninety-eight patients with small cell carcinoma of the bronchus (SCCB) were treated with a combination of cyclophosphamide, methotrexate with calcium leucovorin rescue, and lomustine (CCNU). VP-16-213 was given on relapse. Response rate and survival were analyzed according to extent of tumor, presence of the syndrome of inappropriate antidiuretic hormone production (SIADH), and, in 38 patients, size of intrathoracic tumor as measured by computerized tomographic (CT) scanning. The median survival of the entire group was 34.6 weeks. In patients with limited disease the median survival was 46 weeks compared to 29 weeks for those with extensive disease. This difference in survival between patients with limited and extensive disease was most marked in those showing a partial response (median survival, 45.9 and 28 weeks, respectively). Patients with ectopic antidiuretic hormone production had a poor prognosis even if they had achieved a complete response. Only one partial response to VP-16-213 occurred. There was a strong correlation between initial intrathoracic tumor size as assessed by total cross-sectional area on CT scan and response and survival. When the total area exceeded 30 cm2 there were no complete responders, but there were complete responses in eight of 21 patients when the area was less than 30 cm2. The relationship between intrathoracic tumor size and response rate was present when analyzed according to disease extent, age, sex, and performance status. A clear relationship between total tumor area and survival was also found. When SCCB is treated with chemotherapy alone, the prognosis is better for those patients who present with limited disease, without SIADH, and with small intrathoracic tumor. In this group it is possible that further intensification of therapy may result in prolonged survival.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Small Cell; Cyclophosphamide; Drug Therapy, Combination; Etoposide; Female; Humans; Inappropriate ADH Syndrome; Leucovorin; Lomustine; Lung Neoplasms; Male; Methotrexate; Middle Aged

5 patients with small-cell lung cancer were treated with high-dose methotrexate (1.75-16 g). No significant tumor reduction could be demonstrated. High-dose methotrexate therapy cannot be recommended for the treatment of small-cell lung cancer. Other established and successful regimens are available.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Vincristine

High-dose methotrexate and Leucovorin (calcium folinate) rescue was evaluated as induction chemotherapy in combination with cyclophosphamide, doxorubicin, and vincristine in 21 patients with extensive-stage small cell lung cancer. Nine (42%) of 21 had a complete remission. The median duration of remission has been short (5 months), and attempts are now under way to improve consolidation chemotherapy. In general, the degree of myelotoxicity was not increased by the high-dose methotrexate, although the antitumor activity of the combination appears enhanced. Attempts at further increasing the intensity of this regimen or comparative trials with other therapy appears warranted.

Topics: Adult; Aged; Carcinoma, Small Cell; Drug Therapy, Combination; Female; Humans; In Vitro Techniques; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged

A patient with oat cell carcinoma of the larynx with metastasis to cervical lymph nodes is presented. Treatment with radiation and chemotherapy has achieved a sustained remission. Pretherapy staging and combined modality therapy are discussed.

Topics: Aged; Antineoplastic Agents; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Humans; Laryngeal Neoplasms; Leucovorin; Lymphatic Metastasis; Male; Methotrexate; Neck; Radiotherapy Dosage; Remission, Spontaneous

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Cycle; Cell Survival; Drug Therapy, Combination; Humans; Kinetics; Leucovorin; Lung Neoplasms; Methotrexate

Methodichlorophen was given to 26 patients with terminal malignant disease. Eight patients received adequate doses, and five of them showed objective evidence of tumour regression while three failed to respond. Those who responded included four out of five patients with lung cancer (three with squamous-cell carcinoma and one with oat-cell carcinoma) and a patient with hypernephroma. Two patients with testicular teratomas and one with acute myeloid leukemia failed to respond. The drug may be given safely by mouth to outpatients if certain precautions are taken.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Bone Marrow Diseases; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Chlorobenzenes; Drug Therapy, Combination; Erythema; Headache; Humans; Kidney Neoplasms; Leucovorin; Leukemia, Myeloid, Acute; Lung Neoplasms; Male; Middle Aged; Neoplasms; Pyrimethamine; Pyrimidines; Teratoma; Testicular Neoplasms