Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fludarabine phosphate is the 2-fluoro, 5'-monophosphate derivative of vidarabine (ara-A) with the advantages of resistance to deamination by adenosine deaminase (ADA) and improved solubility. The mechanism of cytotoxic action of the compound appears to involve metabolic conversion to the active triphosphate. Fludarabine phosphate has substantial activity against lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). Its single-agent activity in CLL appears at least comparable to those of other conventional combination regimens. Its activity in Hodgkin's disease, mycosis fungoides, and macroglobulinemia, although suggestive, needs to be further defined and clinical trials are warranted in hairy cell leukemia, prolymphocytic leukemia, and previously untreated myeloma. The compound does not appear active against most common solid tumors. Early clinical trials indicated significant myelosuppression and the potential for severe neurotoxicity. Toxicity on the currently used low-dose schedules includes transient and reversible myelosuppression, nausea and vomiting, diarrhea, somnolence/fatigue, and elevations of liver enzymes and/or serum creatinine. Possible pulmonary toxicity has been suggested in several patients. The currently used low-doses of fludarabine phosphate, even with repeated administration, are well tolerated and appear safe with a negligible risk for severe neurotoxicity. Based on its single-agent activity and tolerability, the Food and Drug Administration recently granted group C designation of the drug for the treatment of patients with refractory CLL outside the clinical trials setting. The use of fludarabine phosphate in combination regimens and its impact on the natural history of the lymphoid malignancies is yet to be determined. Fludarabine phosphate may well occupy a pivotal role in the management of CLL and low-grade NHL.
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PMID:Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. 170 43

Fifty-six patients with Hodgkin's disease in advanced stages (III-IV) were entered in a study aimed to compare standard doses (28 cases) with low doses (28 cases) ABVD regimen. Both groups had similar clinico-pathological features. The group receiving standard doses chemotherapy achieved complete remission rate of 89% versus 85% for the low-doses group. The number of relapses was, respectively, 8 and 9, and the duration of remission was 66 and 57 months, respectively. Presently, 24 patients have died, 11 of the standard doses group and 13 of the reduced doses group. Toxicity was notably higher in the group receiving standard dosage, where fatal myelosuppression was present in two instances. Those data appear to suggest that chemotherapy with reduced doses for Hodgkin's disease can attain similar response rate and survival than those achieved with standard treatment, with the advantages of a lower toxicity.
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PMID:[Hodgkin's disease treated with chemotherapy at reduced dosage]. 170 65

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.
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PMID:Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. 172 Mar 82

Eighty patients with advanced Hodgkin's disease were randomized either to treatment with combination of doxorubicin, bleomycin, vinblastine, and prednisone (ABVP), alternating with lomustine, vincristine, procarbazine, and prednisone (LOPP)--Group A, or to combination of cyclophosphamide, vincristine, procarbazine, prednisone, and low dose of bleomycin (COPP-Bleo)--Group B. Thirty-nine out of 41 patients (95%) in Group A achieved complete remission (CR) as compared to 25 CR in 39 patients (64%) in Group B. Patients with systemic symptoms, bulky disease, and nodular sclerosis achieved significantly more CR after treatment with ABVP/LOPP regimen than with COPP-Bleo regimen. Ninety percent of patients are alive in Group A (median observation time 97+ months) as compared to 58% in Group B (median observation time 97+ months). Ninety-two percent of complete responders are in CR in Group A as compared to 53% of complete responders in Group B. These differences between both groups are significant. More serious (WHO grade III and IV) myelosuppression as well as stomatitis and alopecia were observed in Group A. Gastrointestinal toxicity and neurotoxicity was more frequent in Group A. No patient died due to toxicity in Group A as compared to one patient in Group B. Non-cross-resistant alternating regimen ABVP/LOPP was more effective in the treatment of advanced Hodgkin's disease than the COPP-Bleo regimen, especially for patients with advanced Stage IVB Hodgkin's disease.
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PMID:Comparison of two non-cross-resistant combinations (ABVP/LOPP) with COPP plus bleomycin in the treatment of advanced Hodgkin's disease. 172 64

A total of 136 patients with Hodgkin's disease (HD) seen at a national referral hospital in Kenya over a 15-year period were studied. The overall male-to-female ratio was 2.6:1, with 65% of patients younger than 20 years of age. The bimodal incidence of HD frequently seen in the developed nations was absent, and the histologic pattern of the disease was similar to that seen in other African countries. Fifty percent of patients had advanced-stage disease when first seen. Over two thirds of patients treated had a clinical remission, and the relapse rate in all stages was approximately 30%. Therapy-related complications were common, with frequent myelosuppression and younger patients more susceptible.
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PMID:Hodgkin's disease in Kenya. 173 72

We report the results of two phase II trials of ifosfamide in very high risk patients with either partially responsive or recurrent non-Hodgkin's lymphomas. In the first study, in which patients were extremely heavily pretreated (50 per cent had received a very intensive salvage regimen containing very high dose cyclophosphamide), there were two complete responses, two partial responses and one objective (minimal) response among 14 patients treated. Toxicity was acceptable even in this end-stage patient group. We concluded that ifosfamide is an active agent even in patients with tumours resistant to cyclophosphamide. The second trial was a pilot study in 13 patients of a regimen incorporating VP16, ifosfamide/mesna, and high dose ara-C (VIPA). There were four complete responses, five partial responses and two objective responses. Two patients died in complete remission from toxic complications, while a third, with a stably regressed mediastinal mass died after completion of the protocol. While very toxic, we considered that this regimen was highly effective, and have since incorporated a slightly less intensive combination of the same drugs into the primary therapy of high risk patients. Since the primary toxicity of the VIPA combination was myelosuppression, the use of a modified protocol incorporating colony stimulating factors to ameliorate the side-effects and possibly increase dose rate is worthy of further exploration in patients with recurrent B cell tumours.
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PMID:Ifosfamide in the treatment of high-grade recurrent non-Hodgkin's lymphomas. 174 29

Methotrexate (MTX) is now widely used for the treatment of acute leukemia and non-Hodgkin lymphoma in the pediatric oncology field and is thought to be one of the key drugs for this treatment. A regimen utilizing high dose MTX (HD-MTX) with leucovorin rescue is being investigated as effective chemotherapy in the patients with these kinds of cancer. Relatively large amounts of MTX (225 mg/m2) are given to such outpatients by intravenous push as a course of maintenance therapy. It is said that those amounts will infuse safely. However, we experienced two serious cases-patients T.H. and M.Y.--which developed into severe side effects after this treatment. Both patients showed acute renal failure, severe myelosuppression, erosion around the oral and anal region, and continuous diarrhea. Judging from the serum concentration of MTX, patient T. H. was exposed to more than the maximum allowance serum MTX level for 9.6 days, patient M. Y. for 6.5 days. This suggests physicians must pay attention to the clinical symptoms even after treatment using MTX without HD-MTX.
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PMID:[Clinical evaluation of severe toxicity in two patients with acute lymphoblastic leukemia receiving outpatient methotrexate therapy]. 175 61

Early phase II study of MST-16[4,4-(1,2-ethanediyl) bis (1-isobutoxycarbonyloxy-methyl-2, 6-piperazinedione], a derivative of ICRF-154, on malignant lymphoma was conducted by multi-institutional cooperative group. MST-16 was administered orally at doses of 1,600 mg/body/day for 5 days or 1,200 mg/body/day for 10-14 days, mainly. The number of registered and evaluated patients were 29 and 28, respectively (Hodgkin's disease 3 patients and non-Hodgkin lymphoma 25). Twenty-seven of 28 patients had received prior chemotherapy and/or radiation therapy. Of 28 evaluable patients, overall response rate (CR + PR) was 32.1%. In high-dose administration group, the response rate was not significantly high. The response rate seemed to be high in patients who were treated repeatedly (number of courses greater than 3). Major side effects observed were myelosuppression and gastro-intestinal disorders which were reversible in a rest period. Myelosuppression seemed to be severe in high-dose administration group. This study indicated that MST-16 was a useful agent against malignant lymphoma including primary resistant or relapsed patients, and that the recommended regimen for a late phase II study was considered to be 1,600-2,400 mg/body/day for 5-7 days repeatedly with a pause of several days. Furthermore, the study should be considered at the dose of 3,200 mg/body because half cases administered at this dose showed some response.
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PMID:[Early phase II study of MST-16 (sobuzoxane) on malignant lymphoma]. 195 63

Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue.
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PMID:Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site. 197 51

The treatment of relapsing or refractory high-grade malignant non-Hodgkin lymphoma (NHL) following CHOP chemotherapy remains a challenge for the clinician. In this study, 29 patients with relapsing or refractory high- or refractory low-grade malignant NHL received a combination of mitoxantrone 12 mg/m2 i.v. on days 1-2, cytarabine 100 mg/m2 i.v., b.d. d 1-2, etoposide 100 mg/m2 i.v. d 1-3 and prednisone 100 mg/m2 orally d 1-3 (ENAP). An overall response rate of 55% encouraged us to use ENAP alternated with conventional CHOP chemotherapy in 45 previously untreated NHL patients (35 with high-grade and 10 with "aggressive" low-grade malignant NHL). All patients responded with a complete remission rate (CR) of (27%) and a partial remission rate (PR) of 73% after only one course of ENAP. After a median number of 3.5 ENAP/CHOP courses, the CR and PR rate was 69 and 22%, respectively. Myelosuppression was pronounced and fever of unidentified origin and documented infections followed 59% of all cases given ENAP courses. In the last 19 previously untreated patients mitoxantrone was given at a dose of 10 mg/m2 on d 1 and cytarabine 100 mg i.v., b.d. during d 1-2. Nonhematologic toxicity was mild. We conclude that this novel chemotherapy program is effective both as first-line and salvage treatment in patients with high-grade malignant NHL. Furthermore, ENAP appears clinically to be partly non-cross resistant with CHOP chemotherapy. The dose-limiting toxicity is myelosuppression. The combination should be explored as primary therapy in combination with other chemotherapy or radiotherapy programs.
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PMID:Mitoxantrone, etoposide, cytarabine and prednisone as salvage therapy for refractory non-Hodgkin lymphoma (NHL) and alternated with CHOP in previously untreated patients with NHL. 198 4


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