levoleucovorin and Sarcoma

Sixty-five patients with high-grade soft tissue sarcomas of the extremities were treated in a prospective randomized trial evaluating the efficacy of adjuvant chemotherapy with doxorubicin, cyclophosphamide, and high-dose methotrexate. Local therapy was administered using either amputation or wide local resection plus radiation therapy and the chemotherapy was begun in the immediate postoperative period. Actuarial analysis with median follow-up of 653 days revealed an advantage in continuous disease-free and overall survival in the patient group receiving chemotherapy (P = 0.0008 and P = 0.04, respectively, one-sided Mantel-Haenszel test). The continuous disease-free survival at three years is 92% in the chemotherapy group compared to 60% in the no chemotherapy group. Overall survival is 95% and 74% in these two patient groups. Fifty-eight percent of patients had limb-sparing surgery plus radiation therapy and 42% underwent amputation. In both treatment subgroups analyzed separately, chemotherapy resulted in an improvement in disease-free survival compared to randomized controls not receiving chemotherapy (P = 0.006 and P = 0.04 for groups receiving amputation and limb sparing, respectively). There were no local failures in the patients receiving chemotherapy and two local failures in the no chemotherapy group. The results of this trial confirm the historically controlled pilot trial performed in 26 patients between 1975 and 1977. A current update of the patients in the pilot trial, with a minimum four-year follow-up, reveals an improvement in disease-free and overall survival due to chemotherapy (P less than 0.002). Analysis of the previous pilot trial indicates that only few recurrences are seen beyond three years. Thus, it appears that adjuvant chemotherapy should be a part of the treatment adult patients with soft tissue sarcomas of the extremities.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Extremities; Female; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Prospective Studies; Random Allocation; Sarcoma; Soft Tissue Neoplasms

We evaluated the antitumor effect of combined therapy with tegafur/uracil (UFT) plus leucovorin (LV) (UFT/LV) and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly. UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.

Topics: Animals; Antineoplastic Agents; Carcinoma, Lewis Lung; Colonic Neoplasms; Disease Models, Animal; Drug Therapy, Combination; Female; Leucovorin; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Proteoglycans; Sarcoma; Tegafur; Uracil; Xenograft Model Antitumor Assays

Methotrexate nephrotoxicity can lead to delayed methotrexate elimination and the development of life-threatening toxicity, which may not be preventable with the standard rescue agent leucovorin. In preclinical studies, we previously demonstrated that carboxypetidase-G2 (CPDG2) rapidly hydrolyzes methotrexate to nontoxic metabolites. A protocol for the compassionate use of CPDG2 in patients who develop nephrotoxicity while receiving high-dose methotrexate was therefore developed. The pharmacologic and clinical outcome of CPDG2 rescue administered with thymidine and leucovorin in 20 patients is presented here.. Patients with high-dose methotrexate-induced renal dysfunction received one to three doses of CPDG2, 50 U/kg body weight intravenously (i.v.), thymidine 8 g/m2/d by continuous i.v. infusion, and standard pharmacokinetically guided leucovorin rescue. Plasma concentrations of methotrexate and its inactive metabolite 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) were measured before and after CPDG2 using high-pressure liquid chromatography (HPLC). Tolerance of CPDG2 and thymidine, development of methotrexate toxicities, and recovery of renal function were monitored.. Twenty patients who received high-dose methotrexate for osteosarcoma (n = 11), lymphoid cancers (n = 8), and gastric cancer (n = 1) developed nephrotoxicity (median serum creatinine, 3.2 mg/dL) and elevated plasma methotrexate concentrations (median, 201 mumol/L at hour 46). CPDG2 and thymidine rescue was well tolerated and resulted in a rapid 95.6% to 99.6% reduction in the plasma methotrexate concentration. Methotrexate-related toxicity was mild to moderate. Serum creatinine returned to normal values at a median of 22 days.. CPDG2, thymidine, and leucovorin rescue was highly effective in 20 patients at high risk for developing life-threatening methotrexate toxicity after the onset of methotrexate-induced nephrotoxicity and delayed methotrexate excretion.

Topics: Adolescent; Adult; Antidotes; Antimetabolites, Antineoplastic; Carboxypeptidases; Child; Child, Preschool; Female; Humans; Infant; Kidney; Kidney Diseases; Leucovorin; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sarcoma; Thymidine

This is a retrospective review of five children with post-irradiation bone sarcoma (PIS). Age at PIS onset ranged between 10 and 17 years (median 11). They were treated with a chemotherapy regimen, similar to that in use for primary osteogenic sarcoma, consisting of vincristine and high-dose methotrexate alternated with cisplatinum and ifosfamide, given for 12 months.. In all children chemotherapy induced a complete clinical remission. Four of them were alive in continuous complete remission at 1, 2, 4, and 12 years from the diagnosis of bone sarcoma. One girl recurred 3 years from PIS diagnosis and was salvaged by repeating the same chemotherapy program: she remained alive in second complete remission 8 years from relapse.. In spite of an intensive treatment previously given for the primary tumor, this drug schedule proved to be feasible and short-term side effects were manageable. Chemotherapy alone, using an intensive regimen effective for primary osteogenic sarcoma, may be an adequate therapy for childhood post-irradiation sarcoma.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Cisplatin; Female; Humans; Ifosfamide; Leucovorin; Male; Methotrexate; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Remission Induction; Retrospective Studies; Rhabdomyosarcoma; Sarcoma; Sarcoma, Ewing; Survivors; Vincristine

The case of an extensive pulmonary artery sarcoma managed by radical excision and homograft reconstruction followed by aggressive chemotherapy and irradiation with prolonged survival is presented. Pulmonary artery sarcomas are reviewed with emphasis on the diagnosis and management of these usually fatal tumors.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cardiopulmonary Bypass; Doxorubicin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Pulmonary Artery; Sarcoma; Vascular Diseases

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Doxorubicin; Humans; Leucovorin; Methotrexate; Sarcoma

Twenty-six evaluable patients with advanced soft tissue and bony sarcomas refractory to chemotherapy were treated with vincristine plus high-dose methotrexate and leucovorin rescue. A 14% response rate was observed among 14 patients presenting with refractory soft tissue sarcomas. No responses were observed among 12 patients with bony sarcoma. Toxic reaction with nausea, vomiting, nephrotoxicity, and myelosuppression was manageable. While this study did demonstrate activity of this regimen in doxorubicin-refractory patients, the duration of the responses was relatively brief. Thus, the clinical utility of such a regimen is questionable.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Dose-Response Relationship, Drug; Drug Evaluation; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Sarcoma; Vincristine

Response rates of metastatic soft part sarcomas to chemotherapy have varied from 27 and 44% for our ALOMAD and OMAD protocols to 46-55% reported for CYVADIC. The present combination, CYOMAD, consists of the induction part of ALOMAD (vincristine, high-dose methotrexate with citrovorum factor rescue, Adriamycin and DTIC) alternating with a condensed version of CYVADIC (cyclophosphamide, vincristine, adriamycin and DTIC). Forty-one patients with advanced soft-part sarcomas were entered on the CYOMAD program of whom 36 were considered evaluable. Complete responses (CR) were seen in four patients had partial (PR) in five patients for a major response rate of 25%. Responders had an overall longer survival than nonresponders (20 versus 13 months). Toxicity was substantial with both gastrointestinal side effects and myelosupression common. Possible Adriamycin cardiotoxicity was noted in four patients. Cyomad offered no therapeutic advantage over previous protocols and was even less well tolerated than some.

Topics: Adolescent; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dacarbazine; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Heart Diseases; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Nausea; Sarcoma; Vincristine; Vomiting

Of 12 adult patients with high-grade soft tissue sarcoma receiving adjuvant chemotherapy and at risk for 36-84 months, 9 (75%) remain metastasis free and 10 (83%) have adequate local disease control with limb preservation. This is significantly better (P greater than 0.015) than a comparable "historic" control of 48 previously treated patients. The results correlate well with the few similar studies reported.

Topics: Adult; Aged; Antineoplastic Agents; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Pilot Projects; Radiography; Sarcoma; Vincristine

Sixty-four adult patients with soft-tissue sarcomas received adjuvant chemotherapy with a six-drug combination regimen after surgery. Seventy percent remain free of disease with a median follow-up of 50 months. Only seven patients have died of their disease, all within the first 24 months after surgery. Most patients experienced severe nausea and vomiting secondary to the actinomycin D and dacarbazine parts of the protocol, and three patients experienced frank Adriamycin cardiomyopathy. Toxicity from this combination was otherwise mild. The 58% recurrence rate of 12 patients who discontinued therapy early because of nausea was significantly greater than the 23% rate for those who completed or relapsed on therapy (P = 0.01). Adjuvant chemotherapy should be considered after surgery for patients with soft-part sarcomas, especially those with high-grade tumors that have a considerable risk of recurrence.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Dacarbazine; Dactinomycin; Doxorubicin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Sarcoma; Soft Tissue Neoplasms; Vincristine

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Child; Drug Evaluation; Drug Therapy, Combination; Folic Acid Antagonists; Head and Neck Neoplasms; Humans; Leucovorin; Leukocyte Count; Melanoma; Neoplasms; Platelet Count; Pyrimethamine; Sarcoma

Topics: Adolescent; Adult; Antineoplastic Agents; Child; Child, Preschool; Chlorambucil; Cyclophosphamide; Dacarbazine; Dactinomycin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Neoplasm Staging; Sarcoma; Soft Tissue Neoplasms; Urogenital Neoplasms; Vincristine

Surgical extirpation of the primary tumor has traditionally been utilized as initial treatment for sarcomas in children. The present report, however, demonstrates that sarcomas are optimally treated by means of a coordianted multidisciplinary approach. The latter offers the potential for achieving improved survival and preservation of organs and limbs, particularly for structures of the head and neck, for extremities, and in the genitourinary system.

Topics: Adolescent; Age Factors; Antineoplastic Agents; Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Dactinomycin; Doxorubicin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Leucovorin; Lymphatic Metastasis; Male; Methods; Methotrexate; Neoplasm Metastasis; Osteosarcoma; Rhabdomyosarcoma; Sarcoma; Sarcoma, Ewing; Soft Tissue Neoplasms; Vincristine

In clinical studies performed during 111 infusions of high dose methotrexate (MTX) we have evolved a clinical and laboratory protocol which permits such therapy without prohibitive risk to the patient. The plasma MTX data obtained indicate that pharmacokinetic disposition is dose related during these infusions and that such data are useful in identifying patients at risk from serious toxicity.

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Drug Therapy, Combination; Humans; Leucovorin; Melanoma; Methotrexate; Middle Aged; Neoplasms; Sarcoma; Soft Tissue Neoplasms

Surgical techniques for the selective administration of anti-cancer drugs is presented. These isolated-perfusion or intra-arterial infusion procedures have achieved significant palliation for many patients with advanced cancer. When used in conjunction with surgical excision of certain early skin cancers, such as aggressive forms of malignant melanoma of the extremities, improved cure rates may be achieved.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Chemotherapy, Cancer, Regional Perfusion; Drug Therapy, Combination; Extremities; Female; Head and Neck Neoplasms; Humans; Injections, Intra-Arterial; Leucovorin; Male; Melanoma; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Sarcoma; Sarcoma, Kaposi; Skin Neoplasms

Topics: Humans; Leucovorin; Methotrexate; Neoplasm Metastasis; Remission, Spontaneous; Sarcoma

Topics: Antineoplastic Agents; Carcinoma; Chemotherapy, Cancer, Regional Perfusion; Fluorouracil; Head; Head and Neck Neoplasms; Humans; Leucovorin; Melanoma; Melphalan; Methotrexate; Mouth Neoplasms; Nasopharyngeal Neoplasms; Paranasal Sinus Neoplasms; Sarcoma; Thiotepa; Vinblastine