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

Thirty-nine patients with advanced Hodgkin's disease (H.D.) resistant to standard combinations of cytotoxic drugs were treated with C.C.N.U., vinblastine and bleomycin (C.V.B.). Ten patients (25%) achieved complete remission (C.R.) and seven of these are still in C.R. at the time of this report. A further 23 patients (59%) achieved partial remissions. The overall response-rate was thus 85%. C.C.N.U. caused less nausea and vomiting than that usually associated with nitrogen mustard. C.C.N.U. and vinblastine caused myelosuppression, but C.V.B. could be administered every 4 weeks to 21 (54%) of the 39 patients. A combination of cytotoxic drugs such as C.V.B. may be preferable to single agents in the treatment of patients with advanced resistant H.D.
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PMID:Combination therapy for advanced resistant Hodgkin's disease. 5 20

Twenty-four patients with far advanced malignant tumors, resistent to established chemotherapy,, were treated with the combination of MNU and Cyclophosphamide. The drugs were administered in six-day cycles sequentially. MNU in doses of 4 mg/kg body weight and Cyclophosphamide in doses of 8 mg/kg body weight were given. Results of treatment showed response (greater than 50% tumor regression) in 10 (42%) of the 24 treated patients. Seven remissions were complete and three partial. Patients with Hodgkin's disease, malignant melanoma and breast cancer responded to this combination chemotherapy. Objective remissions were obtained also in five of thirteen patients with primary or metastatic brain tumors and in five of nine patients with pulmonary metastases. Nausea and vomiting were the main toxic effects, especially after injections of MNU. Myelosuppression was noted in about 50% of treated patients. Since this combination of cytostatics showed significant antitumor activity, further investigations are necessary on a larger number of patients and in other types of malignant tumors.
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PMID:Combination chemotherapy with 1-methyl-1-nitrosourea (MNU) and cyclophosphamide in solid tumors. 14 13

Chlorozotocin was given to 37 patients with advanced malignant tumors in a daily X 5 schedule at 6-week intervals. Total iv doses for each course ranged from 75 to 200 mg/m2. Myelosuppression was dose-limiting, with a platelet count depression regularly observed at doses of greater or equal to 150 mg/m2; leukopenia occurred only at the highest dose level. Nausea and vomiting were mild and uncommon. No hyperglycemia or adverse drug-related effects on renal or hepatic function were observed. No major antitumor activity occurred; however, three patients with renal cell carcinoma and one patient each with lung cancer, ovarian carcinoma, and Hodgkin's disease had minor objective decreases in tumor size. A dose range of 150--200 mg/m2 iv for each 5-day course is recommended for phase II studies.
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PMID:Phase I trial of chlorozotocin. 15 63

The effects of iv administered piperazinedione were studied in 28 evaluable adult and eight evaluable pediatric patients with advanced cancer. Piperazinedione produced predictable myelosuppression of moderate degree at dosages of 3--3.5 mg/m2/day X 5 days by iv injection. When given in this manner, nausea and vomiting did not occur. Single iv doses of 10--15 mg/m2 produced mild-to-moderate nausea and vomiting and mild myelosuppression. Thrombocytopenia was more severe than leukopenia in both schedules. The drug produced comparable dose-related effects in adults and children. Although no therapeutic response was observed in the adults, a partial remission of 6 months' duration was seen in one child with Hodgkin's disease.
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PMID:Phase I evaluation of piperazinedione in patients with advanced cancer. 36 94

The Southwest Oncology Group has evaluated the activity of cis-dichlorodiammineplatinum(II) at a dose of 75 mg/m2 given as an iv bolus injection every 3 weeks to 25 fully and partially evaluable patients with advanced Hodgkin's disease and non-Hodgkin's lymphoma. One complete response, two partial responses, and one improvement less than a partial response were noted. Myelosuppression, in the form of leukopenia and thrombocytopenia, was identified and seemed to be more prevalent and more severe than in previous studies. We have attributed this to the extensive prior treatments which these patients had received and to the presence of tumor-bearing marrow which was observed in some of them. The anticipated toxic effects which were noted included nausea and vomiting, anorexia, diarrhea, renal injury, and hyperuricemia. The precise role of cis-dichlorodiammineplatinum(II) in the management of human lymphomas awaits elucidation.
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PMID:Phase II evaluation of cis-dichlorodiammineplatinum(II) in lymphomas: a Southwest Oncology Group Study. 49 59

Chromomycin A3 was given to 43 patients with metastatic cancer in order to determine the tolerable dose when the drug was administered on an every-other-day dose schedule for a total of five iv push injections, with the course of therapy being repeated every 4 weeks. At least three patients were entered at each dose level, graduated in 0.1-mg/m2 increments between 0.7 and 1.6 mg/m2. The most common (19 patients) side effect was nausea and/or vomiting, but this was usually mild, lasted for a few hours, and diminished in severity with repeated injections. Skin necrosis due to drug extravasation was a problem early in the study, but was eliminated by injecting the drug through iv tubing. Transient elevations in SGOT and alkaline phosphatase levels were observed, but proved not to be of serious consequence. Renal toxicity proved to be the limiting factor in therapy. However, a dose level of 1.3 mg/m2 was found to be a tolerable level of drug administration in previously untreated patients. Objective tumor responses were noted in four patients (Hodgkin's disease, embryonal rhabdomyosarcoma, adenocarcinoma of the lung, and malignant melanoma).
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PMID:Phase I alternate-day dose study of chromomycin A3. 103 32

Thirty-seven children with various malignant neoplasms were treated with 1-acetyl-2-picolinoylhydrazine. Complete regressions were documented in one child with embryonal rhabdomyosarcoma, in one child with generalized histiocytosis-X, and in one child with Hodgkin's disease. One patient had renal failure while receiving the drug but no conclusive cause and effect relationship could be established. Toxic effects otherwise were mild and consisted primarily of nausea and vomiting.
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PMID:Clinical trials with 1-acetyl-2-picolinoylhydrazine (NSC-68626) in children. 109 92

The scheduling of chemotherapeutic agents may be important in optimising their antitumour actions. This has been explored in non-Hodgkin lymphoma, osteogenic sarcoma and bladder cancer with improved results using intensive, weekly dosing schemas. We began a phase II study of cisplatin, 5-fluorouracil and vinblastine in non-small cell lung cancer (NSCLC) on a weekly schedule. 38 patients with advanced or metastatic NSCLC were entered; 32 are evaluable for response. 11 patients were treated with 5-fluorouracil 1.5 g/m2 and vinblastine 4 mg/m2 by 24-h continuous infusion, and cisplatin 30 mg/m2 over 30 min, 6-8 h after the start of the infusion. Because of prohibitive myelotoxicity, the next 27 patients received 5-fluorouracil 1.2 g/m2 and vinblastine 3 mg/m2. None had had prior chemotherapy while 6 had had previous radiation therapy. Myelosuppression was the predominant toxic effect. Other side-effects included neuropathy, diarrhoea, mucositis, nausea and vomiting. 32 patients are evaluable for response: there have been 14 partial remissions (44%). Responses have occurred chiefly in lung and lymph nodes. The median survival on this study is 7 months, and responders did not live longer than non-responders. While this regimen is well tolerated by the majority of patients and has a response rate comparable to other active regimens identified in single institution studies, survival does not appear to be enhanced. We conclude that the schedule manipulation described here does not enhance the therapeutic index of these drugs in NSCLC.
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PMID:Phase II study of weekly 5-fluorouracil, cisplatin and vinblastine in advanced non-small cell lung cancer. 166 16

MOPP (mechlorethamine, vincristine, procarbazine, prednisone) was the first successful regimen for the treatment of Hodgkin's disease. It has the longest period of follow-up and is best studied as to its benefits and acute and long-term side effects. The acute toxicity of the side effects, including nausea and/or vomiting, hair loss, and myelosuppression, may have been reason to modify doses of nitrogen mustard, an agent whose dose intensity may be critical in achieving long-term benefits. The substitution of chlorambucil and vinblastine in the ChlVPP (chlorambucil, vinblastine, procarbazine, prednisone) program has relieved all of these acute toxicities, except myelosuppression. The long-term toxicity of sterility, especially in males, and myelodysplasia is most likely due to alkylating-agent toxicity and would not be influenced by the various MOPP variants, such as MVPP (mechlorethamine, vinblastine, procarbazine, prednisone), ChlVPP, and COPP (chlorambucil-vincristine, procarbazine, prednisone). Doxorubicin-containing regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and ABDIC (doxorubicin, bleomycin, dacarbazine, lomustine, prednisone), have been second-line treatments that have significant antitumor effect and, as such, have resulted in few, if any, long-term cures in most series. ABVD has been incorporated into alternating MOPP/ABVD schemes or in hybrids that attempt to offer all active agents, such as MOPP/ABV. The initial experience has been encouraging with high and durable complete remissions (CRs). MOPP/ABVD x 12(1) and MOPP-2/ABVD-2(2) have been compared with MOPP alone with a significant superiority for the alternating regimens. Other randomized trials have not shown any superiority for the alternating program. The Cancer and Leukemia Group B (CALGB) has compared MOPP with MOPP/ABVD given with a third arm of ABVD alone. The complete response and time-to-treatment failure rates for MOPP/ABVD and ABVD alone were superior to those for MOPP. Significant modifications of MOPP doses may explain the differences, since only 20% of patients were receiving full doses of nitrogen mustard by the sixth dose. ABVD has unique toxicity, and myelodysplasia and sterility are not seen. Pulmonary fibrosis with radiation and bleomycin is unique to ABVD, as shown in the ABVD experience at the NCl (Milan). Can ABVD be improved? The demonstrated single-dose activity of etoposide in Hodgkin's disease has prompted its inclusion in second-line programs, such as EVA (etoposide, vincristine or vinblastine, doxorubicin). The second-line response rates in the St Bartholomew's (London, England) series (where vincristine was used) was 11 of 19 patients (58%);3 in the ongoing CALGB trial of EVA (vinblastine combination), the response rate is 67%. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Can MOPP be replaced in the treatment of advanced Hodgkin's disease? 168 9

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


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