Treatment of Burkitt's tumor with cyclophosphamide.
TL;DR: This study showed that single doses of CTX are capable of inducing long remissions in patients with localized disease and the prognosis is improved in stage III patients who undergo surgical reduction of tumor bulk prior to chemotherapy.
Abstract: The results of therapy of 57 previously untreated patients with Burkitt's tumor seen over a 2-year period at the Lymphoma Treatment Center, Kampala, Uganda are reported. Thirty-seven patients were randomized to either a single dose or multiple doses of intravenous cyclophosphamide (CTX) 40 mg/kg. Ten of 11 patients with localized (stage I-II) disease have continued in complete remission regardless of drug schedule. Among stage III patients, remission duration was shorter and relapse was more common in the group receiving a single dose. Intrathecal chemotherapy using methotrexate and cytosine arabinoside was successfully employed in the management of 12 patients with malignant cells in the cerebrospinal fluid. However, more aggressive and prolonged therapy is indicated to prevent relapse. Secondary chemotherapy using vincristine, methotrexate, and cytosine arabinoside produced complete responses in 90% of patients relapsing on multiple-dose CTX. This study showed that: 1. single doses of CTX are capable of inducing long remissions in patients with localized disease; 2. multiple doses of CTX do not appear harmful in the maintenance of remissions in patients with localized tumors; 3. multiple doses of CTX result in fewer relapses and longer remissions in patients with visceral (stage III) disease compared with a single-dose regimen; 4. the prognosis is improved in stage III patients who undergo surgical reduction of tumor bulk prior to chemotherapy; and 5. recognition and aggressive treatment of patients in relapse, particularly those with central nervous system involvement, are important considerations in the long term management of Burkitt's tumor.
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TL;DR: It is concluded that vigorous treatment of leptomeningeal metastases with intrathecal chemotherapeutic agents improves symptomatology in some patients, and at times prolongs survival.
Abstract: The clinical findings and response to treatment of leptomeningeal metastases from solid tumors are analyzed in 90 patients treated at Memorial Sloan-Kettering Cancer Center during the period from January 1975 to February 1980. Patients included those who had either typical clinical findings of leptomeningeal tumor or conclusive laboratory evidence supporting the diagnosis. Carcinoma of the breast (46 patients), lung (23 patients) and melanoma (11 patients) were the common primary tumors. Symptoms of leptomeningeal metastasis occurred as the presenting sign in five patients and as late as ten years after the primary tumor was diagnosed in four other patients. Most patients had active systemic disease outside the nervous system. Signs and symptoms could be classified as involving either the brain, cranial nerves, or spinal nerves. Most patients had either symptoms or signs in more than one area at the time the diagnosis was established. The initial spinal fluid examination was abnormal in all but three patients, but only 49 had cytologic evidence of leptomeningeal metastases. Repeated spinal fluid assay yielded a positive cytology in 82 patients. Measurement of biochemical markers, including beta-glucuronidase, carcinoembryonic antigen and lactic dehydrogenase, assisted in the diagnosis. Approximately half of the patients treated by intraventricular methotrexate experienced improvement or stabilization of neurological symptoms for more than a month; median survival was 5.8 months after diagnosis, with a range of 1--29 months. In 18 patients disease was limited to the nervous system, and median survival was eight months, with four patients surviving one year and two patients for two years. Side effects of therapy were, for the most part, minor. We conclude that vigorous treatment of leptomeningeal metastases with intrathecal chemotherapeutic agents improves symptomatology in some patients, and at times prolongs survival.
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TL;DR: Now that the chemotherapeutic tools are sharpened, their use in combinations with other modalities in the previously unfamiliar setting of the patient with early stages of the disease promises to lead to an even more exciting chapter in clinical cancer research in the next decade.
Abstract: In a period of a little over 20 years, chemotherapy of cancer has evolved from a period of empiricism with little impact on the cancer problem to become part of a sound medical discipline with firm scientific underpinning playing an increasingly important role in the control of cancer. This progress has come from an increasing knowledge of cancer biology and pharmacology and the application of this knowledge to improved design of clinical trials, with due consideration to the intricacies of the natural history of each disease in question. Now that the chemotherapeutic tools are sharpened, their use in combinations with other modalities in the previously unfamiliar setting of the patient with early stages of the disease promises to lead to an even more exciting chapter in clinical cancer research in the next decade.
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TL;DR: The potential for cyclophosphamide-induced cancers, particularly in the bladder, must be recognised and this agent remains a highly effective drug in many situations.
Abstract: Cyclophosphamide, an orally active alkylating agent, is widely used to treat a variety of malignant and nonmalignant disorders. Although it has some tumour selectivity, it also possesses a wide spectrum of toxicities. The requirement of metabolic activation before cyclophosphamide exerts either its therapeutic or toxic effects is well established, but has not led to effective counter-measures. Clinically, damage to the bladder (haemorrhagic cystitis), immunosuppression (when not desired) and alopecia are the most significant toxicities associated with cyclophosphamide. Cardiotoxicity is also a possibility when very high doses are given. Preventing these toxicities has focused on modifications of the treatment regimens and, in the case of haemorrhagic cystitis, the administration of a drug which is excreted in the urine where it inactivates the bladder-toxic species. As treatment regimens for cancer become more effective in prolonging a patient's life, and as cyclophosphamide receives increasing use for nonmalignant disorders, the potential for cyclophosphamide-induced cancers, particularly in the bladder, must be recognised. Although the toxicities associated with cyclophosphamide are serious, this agent remains a highly effective drug in many situations. Research on the pathways which play an important role in activating this drug may improve our ability to target particular diseases and decrease unwanted side effects.
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TL;DR: Available evidence suggests that, with African lymphoma, not only can long‐term remissions be obtained with no more than two administrations of chemotherapy but further dosage may reduce rather than increase the prospects of success.
Abstract: Available evidence suggests that, with African lymphoma, not only can long-term remissions, believed to amount to cures, be obtained with no more than two administrations of chemotherapy but further dosage may reduce rather than increase the prospects of success. The possible implications of this observation are discussed.
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Journal Article•
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TL;DR: Thirty-five of 77 patients with Burkitt’s lymphoma presented or developed evidence of central nervous system involvement by tumor, which points to direct tumor extension to intracranial structures (duraarachnoid) as the pathogenesis of these lesions.
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TL;DR: On avance l'hypothese that cette tumeur montre generalement une forte proliferation cellulaire, associee a un taux de mortalite cellulaires eleve.
78 citations