levoleucovorin and Femoral-Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Camptothecin; Cisplatin; Combined Modality Therapy; Deoxycytidine; Doxorubicin; Etoposide; Femoral Neoplasms; Gemcitabine; Head and Neck Neoplasms; Humans; Ifosfamide; Irinotecan; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoadjuvant Therapy; Osteosarcoma; Palliative Care; Salvage Therapy; Scalp; Skin Neoplasms; Thoracotomy

The value of adjuvant chemotherapy in primary osteogenic sarcoma (OSA) is still considered controversial by some. One reason may be that various reported series include patients with widely varying prognostic variables. To address this, the effect of chemotherapy on the continuous disease-free (CNED) survival was analyzed in 100 patients aged 21 yr or less with OSA of the femur. This classically poor prognostic group of patients represented 51% of all primary OSA seen at the Memorial Sloan-Kettering Cancer Center during the study interval. This study includes all patients aged 21 yr or less with fully malignant (Grade III-IV/IV) OSA of the femur and no metastases treated from November 1973 through November 1981. The first (T-4) protocol (31 patients) consisted of high dose methotrexate (HDMTX) with leucovorin rescue, cyclophosphamide (Cyc), and adriamycin. In the second (T-7) protocol (23 patients) the dose of HDMTX was increased to 12 g/m2 for prepubescent patients, and bleomycin, Cyc, and dactinomycin replaced Cyc. The current (T-10) protocol (46 patients) uses the same CT as T-7, but patients not having a complete response of the primary tumor to preoperative CT receive additional cisplatinum (120 mg/m2) with adriamycin (30 mg/m2/day for two consecutive days). In 31 patients treated with T-4 the CNED survival was 32% with a minimum follow up of over 7 yr. On T-7, 15/23 patients with femur primaries had a CNED survival of 65% with all of the surviving patients followed for more than 5 yr. The addition of cisplatinum in T-10 has resulted in CNED survival rate of 77% in 34/44 patients (excluding two patients that died CNED during and after treatment); the median follow-up patients who are alive CNED is 33 months, with a minimum of 2 yr follow up on the last patient entered.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Child, Preschool; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Dactinomycin; Doxorubicin; Female; Femoral Neoplasms; Humans; Leucovorin; Male; Methotrexate; Osteosarcoma; Premedication; Prognosis

Topics: Amputation, Surgical; Bone Neoplasms; Clinical Trials as Topic; Drug Therapy, Combination; Femoral Neoplasms; Follow-Up Studies; Humans; Injections, Intramuscular; Injections, Intravenous; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Time Factors; Vincristine

Acute renal failure induced by methotrexate (MTX) can be lethal because renal excretion of the drug can be delayed. Pre-existing renal impairment, abstention, or underdosage of folinic acid and inadequate hydration facilitate toxicity. The prolonged high serum levels of MTX result in severe mucositis and pancytopenia, but strategies useful to accelerate MTX removal have not been universally accepted. We report a case of a 13-year-old girl with osteosarcoma who was treated with high-dose MTX because of thoracic tumor recurrence. No side effects were observed after 2 cycles of high-dose MTX; however, after the third cycle there was a delayed MTX elimination followed by clinical toxicity. Forty hours post-MTX infusion the serum level of MTX was 5.39 x 10(-4) mol/L. Treatment was based on symptomatic measures, such as maintenance of an abundant and alkaline diuresis and parenteral administration of folinic acid. Concomitantly, plasma exchange was employed to accelerate MTX removal and reduce its toxicity. After 24 days, she was discharged from the hospital, and her renal function recovered gradually.

Topics: Acute Kidney Injury; Adolescent; Antimetabolites, Antineoplastic; Diuresis; Female; Femoral Neoplasms; Humans; Leucovorin; Methotrexate; Osteosarcoma; Plasma Exchange; Thoracic Neoplasms

A 17-year-old boy suffered from osteosarcoma in his left distal femur. He was treated with 4 courses of HD-MTX preoperatively, then a wide resection and replacement with endprosthesis was performed. After surgery, 4 more courses of HD-MTX were administered. In the last course of HD-MTX, the serum level of MTX had not decreased to a safe level after 48 hours following MTX administration. Liver and renal dysfunction then occurred, so massive leucovorin rescue and hemoperfusion were done. Fortunately, all complications disappeared. The patient is alive and well, and has been disease free for six years since surgery.

Topics: Adolescent; Antimetabolites, Antineoplastic; Arthroplasty, Replacement, Knee; Combined Modality Therapy; Femoral Neoplasms; Hemoperfusion; Humans; Leucovorin; Male; Methotrexate; Osteosarcoma; Vincristine

Ninety-three cases of primary malignant bone tumors of the limbs were treated for 651 times with preoperative and postoperative HD-MTX-CFR regimen. A number of toxic side reactions appeared, most of which were those of the digestive tract. The side reactions treated symptomatically subsided uneventfully All cases were followed up for 5-7 years, 36 patients died and 57 survived with a 5-year survival rate of 61.3%. A new method to limb salvage was used in 44 cases: the bone segment with tumor was amputated, and replanted back after inactivation with alcohol excision. The five-year survival rate was 63.6%. The excellent results of treatment gave the patients new hope dispelling the misgivings of becoming disabled.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Chemotherapy, Adjuvant; Child; Child, Preschool; Doxorubicin; Female; Femoral Neoplasms; Follow-Up Studies; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Osteosarcoma; Tibia

Methotrexate toxicity is rare but extremely severe. When complete, it consists of ulcerations of the gastrointestinal mucosae responsible for necrotizing enteritis, erythroderma, bone marrow aplasia, interstitial pneumonia, hepatitis and organic renal failure with diuresis. Toxicity is facilitated by pre-existing renal impairment, third sector and abstention or underdosage of foliculinic acid prescribed as antagonist. The diagnosis rests on serum assays, the results of which must be interpreted taking into account the assay method and the time elapsed between the injection of methotrexate and its assay in serum. The multivisceral pathology observed may totally regress, as in the case reported here. Treatment is based on symptomatic measures, starting with maintenance of an abundant and alkaline diuresis, and on the parenteral administration of folinic acid in doses that vary with the authors.

Topics: Acute Kidney Injury; Chemical and Drug Induced Liver Injury; Dermatitis, Exfoliative; Enteritis; Femoral Neoplasms; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Osteosarcoma; Poisoning; Pulmonary Fibrosis

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Femoral Neoplasms; Humans; Leucovorin; Male; Methotrexate; Osteosarcoma; Remission Induction

The interim results of the use of high-dose methotrexate with leucovorin rescue for the treatment of 26 patients with osteogenic sarcoma are discussed. Preoperative chemotherapy was followed by marked regression of primary tumor in one out of seven patients with localized disease. In that group, metastasis-free period lasted 2, 3, 10+, 12, 17+ and 24+ months. Response was observed in two out of 19 (10.6%) cases of metastases. Toxic side-effects were moderate and were mainly nausea (38.5% of patients), vomiting (26.9%), elevation of serum transaminase levels (38.5%) and fever (30.7% of cases).

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Drug Evaluation; Female; Femoral Neoplasms; Humans; Humerus; Leucovorin; Lung Neoplasms; Male; Methotrexate; Osteosarcoma; Preoperative Care; Tibia

There are still some controversy on the role of adjuvant chemotherapy in the treatment of osteogenic sarcoma, and no relevant report has been published in Chinese medical literature. In this paper 15 patients with osteogenic sarcoma treated from March 1982 to March 1986 by high dose MTX with citrovorum factor rescue after surgery are reported. Another 15 patients treated by surgical amputation alone during the same period served for comparison. The sex, age and site of the tumor in the two groups were comparable. In the treated group, MTX 0.7-1.4 g/m2, averaged 0.92 g/m2 were given intravenously, followed by citrovorum factor rescue, once a month for 2-12 injections. 12 patients (80%) in this group were given more than 4 injections. All patients tolerated the treatment well and no death was ascribed to the treatment. The patients were followed for 7-48 months, in the HD-MTX treated group, 1 patient was lost in the follow up, 9 died and 5 were still alive (35.7%). In the comparison group, 2 were lost, 11 died and only 2 were still alive (15.4%). The 2 year survival rate for the treated group was 57.1% and 30.8% for the comparison group (P greater than 0.05). The authors suggest that the dose of MTX be increased and combined with other cytostatic drugs like doxorubicin and cisplatin when necessary for better results. Adjuvant chemotherapy has definite value in the treatment of osteogenic sarcoma if adequate dose and protocols are used. However, the best adjuvant chemotherapy program for Chinese patients still remains to be studied.

Topics: Adolescent; Adult; Amputation, Surgical; Bone Neoplasms; Child; Combined Modality Therapy; Female; Femoral Neoplasms; Humans; Leucovorin; Male; Methotrexate; Osteosarcoma; Postoperative Care; Retrospective Studies; Tibia

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Femoral Neoplasms; Follow-Up Studies; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Osteosarcoma; Postoperative Care; Premedication

Seven patients have been treated for malignant fibrous histiocytoma (MFH) of bone since the end of 1977. One patient received no chemotherapy, and one did not complete attempted chemotherapy. Both died, 7 and 51 months after diagnosis, respectively. The remaining five patients completed chemotherapy. Two first underwent a primary amputation, whereas the other three received primary chemotherapy with histologic evaluation of the effect. These patients showed a complete remission. The five patients who completed chemotherapy are all still alive, without indications of metastases or local recurrence. Although the number of cases is small, a 25- to 58-months (mean, 45) survival, in five patients treated either with chemotherapy alone or chemotherapy and surgery, is surprisingly good in view of previous experience with this tumor. In some of these patients, the authors were able to document an absence of any viable tumor following chemotherapy.

Topics: Adolescent; Adult; Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Cyclophosphamide; Dacarbazine; Doxorubicin; Female; Femoral Neoplasms; Follow-Up Studies; Histiocytoma, Benign Fibrous; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Tibia; Vincristine

High-dose methotrexate with citrovorum factor "rescue" (MTX-CF) produced an apparent complete response of the primary tumor in three patients with osteosarcoma. The response was sustained with MTX-CF, intra-arterial cis-diamminedichloroplatinum II (CDP) and Adriamycin (doxorubicin) for 18 months. Treatment was then electively discontinued. Local recurrence occurred in two patients, 6 and 4 months later, respectively. MTX-CF was reinstated and a complete response was again achieved in one patient. This has been maintained for 15+ months with MTX-CF and intra-arterial CDP administered for 13 of the 15+ months. Reinduction with MTX-CF failed in the second relapsed patient but an apparent remission was again achieved with radiation and intra-arterial CDP. This has been maintained with intravenous CDP, cyclophosphamide and phenylalanine mustard for 14+ months. A complete response in the primary tumor was still present in the nonrelapsed patient, 42 months from diagnosis. All patients have remained free of pulmonary metastases, 40+ to 42+ months from diagnosis.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Female; Femoral Neoplasms; Follow-Up Studies; Humans; Ilium; Infusions, Intra-Arterial; Leucovorin; Male; Methotrexate; Neoplasm Recurrence, Local; Osteosarcoma; Tibia

Two patients treated with high dose methotrexate otrexate with citrovorum rescue (HDMTX-CF) for osteogenic sarcoma developed the acute onset of neurologic deficits. Prior to the onset of symptoms, one child suffered brief episodes of altered consciousness. Both patients developed hemiparesis and then steadily improved over 72 hours. Laboratory evaluations disclosed normal coagulation parameters and nontoxic serum methotrexate levels at onset of symptoms. Computed tomography in one child disclosed a large low absorption abnormality. This patient represents the first reported case of positive radiologic findings associated with this syndrome. The two patients recovered completely and received further HDMTX-CF without sequelae. This condition may result from transient demyelination or embolic cerebrovascular disease.

Topics: Adolescent; Brain; Central Nervous System Diseases; Child; Female; Femoral Neoplasms; Humans; Leucovorin; Methotrexate; Osteosarcoma; Tomography, X-Ray Computed

Topics: Adolescent; Adult; Bone Neoplasms; Child; Child, Preschool; Cisplatin; Doxorubicin; Drug Evaluation; Drug Therapy, Combination; Economics; Femoral Neoplasms; Humans; Humerus; Leucovorin; Methotrexate; Osteosarcoma; Prognosis; Tibia

The case of a six year old girl with metastatic (or primarily multifocal) osteogenic sarcoma is reported, which was treated with chemotherapy only. Within 15 months--the primary tumor regressed and at least a transient inactivation has resulted until now;--the pulmonary metastases showed no progression;--an osteoplastic destruction of the sacrum has completely regressed. At the time of report (15 months after initiation of treatment) neither on X-ray controls nor on bone scan signs of tumor regrowth are evident. The child is without any complaints and the leg has no loss of function.

Topics: Antineoplastic Agents; Child; Doxorubicin; Drug Therapy, Combination; Female; Femoral Neoplasms; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Radiography; Remission, Spontaneous; Sacrum; Vincristine

Topics: Adolescent; Drug Therapy, Combination; Femoral Neoplasms; Humans; Leucovorin; Male; Methotrexate; Osteosarcoma

An unusual neurological syndrome occurred in 4 of 158 patients treated for osteogenic sarcoma with combination chemotherapy. There was an abrupt onset of focal cerebral deficits approximately ten days after chemotherapy with vincristine and high-dose methotrexate plus citrovorum factor rescue. The syndrome was short lived and always occurred early in the course of treatment. Prolonged neurological deficits remained in 2 patients. When similar chemotherapy was reinstituted in the 4 patients, no further neurological complications ensued. Possible causes include a leukoencephalopathy related to methotrexate or an embolic cerebral vasculopathy related to necrotic tumor microemboli emanating from the lungs.

Topics: Adolescent; Adult; Bone Neoplasms; Brain Diseases; Drug Therapy, Combination; Female; Femoral Neoplasms; Humans; Humerus; Leucovorin; Male; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Pelvic Bones; Syndrome; Vincristine

Twenty patients with osteogenic sarcoma of the distal portion of the femur and the proximal portion of the tibia received chemotherapy (vincristine sulfate, methotrexate with leucovorin calcium rescue, [citrovorum factor; folinade calcium], and doxorubicin hydrochloride [Adriamycin]), followed by radical en bloc resection and prosthetic bone replacement. Histologic examination of surgical specimens obtained after chemotherapy showed variable degrees of tumor destruction and, in some cases, massive tumor necrosis, attesting to the profound effects of vigorous chemotherapy. This new therapeutic regimen, when feasible, may prove to be the treatment of choice in osteogenic sarcoma.

Topics: Adolescent; Adult; Amputation, Surgical; Bone Neoplasms; Child; Drug Therapy, Combination; Female; Femoral Neoplasms; Humans; Leucovorin; Male; Methotrexate; Necrosis; Osteocytes; Osteosarcoma; Tibia; Vincristine

Topics: Adolescent; Adult; Aged; Child; Chondrosarcoma; Cyclophosphamide; Doxorubicin; Female; Femoral Neoplasms; Femur; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Postoperative Complications; Prostheses and Implants; Vincristine

Topics: Adolescent; Adult; Drug Therapy, Combination; Femoral Neoplasms; Femur; Humans; Joint Prosthesis; Leucovorin; Male; Methotrexate; Osteosarcoma

Topics: Adolescent; Brain; Brain Neoplasms; Child; Ependymoma; Femoral Neoplasms; Humans; Injections, Spinal; Leucovorin; Male; Methotrexate; Neoplasm Metastasis