摘要:

The advances in therapy for aggressive non-Hodgkin's lymphoma have improved the long-term outlook for patients with this disease. However, many questions still remain such as: which combination chemotherapy protocol is the best? Is is necessary to use a third generation regimen, or is CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) adequate? And finally is the extent of dose intensity that can be achieved with conventional therapy adequate in poor prognosis patients?Although several smaller comparative trials have been done, the four arm trial currently being performed by the South West Oncology Group (SWOG) will represent the largest trial designed to address this issue. One best protocol has not yet been identified as being superior to others for the therapy of patients with aggressive non-Hodgkin's lymphomas. However, certain subsets of patients may benefit from specific protocols. This information can hopefully be gleaned from subset analysis of the SWOG study in the future.At the present time, since one best therapy cannot be identified, physicians should chose a regimen that they are confident in and familiar with it's use. By utilizing a particular regimen, one can minimize the treatment-related mortality and optimize the patient's chance for a good outcome. Subset analysis to identify particular groups that may benefit from higher dose intensity will be an important feature for future analysis.

ISSN:1042-8194    

DOI:10.3109/10428199309149114

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The importance of schedule in the cytotoxic efficacy of etoposide is suggested by the mechanism of action and supported by clinical data in the treatment of small cell lung cancer. To further evaluate the effects of drug schedule, we studied the efficacy of oral etoposide SO mg/m2daily for 21 consecutive days, repeated every 28–35 days, in the treatment of refractory lymphoma. Twenty-five patients were treated; all had received previous chemotherapy and were considered incurable. Fifteen patients (60%) responded to treatment (14 partial responses, 1 complete response), including 5 of 9 patients who had received previous intravenous etoposide. Median response duration was 8 months in patients with low grade lymphoma and 3 months in those with intermediate or high grade lymphoma. The single complete responder remains disease-free 19 months after completion of therapy. Two patients responded to chronic oral etoposide immediately after progression on intravenous etoposide-contain-ing regimens, demonstrating improved efficacy of the chronic schedule. Single agent etoposide, administered at this dose for 21 days, provides an effective and convenient treatment option for patients with indolent lymphoma. Incorporation of this etoposide schedule into combination regimens for aggressive lymphoma is currently under investigation, and preliminary results are reported.We are currently conducting a phase I study using low dose, continuous infusion etoposide (25 mg/m2/day). By avoiding high peak serum levels and maintaining a constant serum level of approximately 1μg/ml, we hope to retain efficacy and minimize or avoid myelotoxicity. Continuous infusion was continued for as long as tolerated. Blood counts were measured weekly, and therapy temporarily interrupted if WBC<2000//μL developed. Six patients with previously treated lymphoma have been treated from 6–54 weeks. Myelosuppression was mild, and no other toxicity except alopecia was observed. Four of 6 responded to therapy. These preliminary data suggest that the toxicity of etoposide can be markedly altered and cytotoxicity can be retained using this method of administration.

ISSN:1042-8194    

DOI:10.3109/10428199309149115

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Idarubicin, a new analogue of daunorubicin, was administered intravenously at a dose of 15 mg/m2to 31 patients with previously treated patients with unfavorable non-Hodgkin's lymphoma. Clinical characteristics included median age 69 years, performance status 1, and prior chemotherapeutic regimens 1. Twenty of the patients were relapsing after prior therapy and 11 were refractory; 29 had received prior anthracycline or anthracenedione.Responses were observed in 43% of patient (3 CR and 10 PR) with a median duration of 10 + months (2–29+ months). Idarubicin was well tolerated with non-hematologic toxicities (nausea/vomiting, mucositis, and anorexia) seen in<50% of patients. Median hematologic values during the first cycle for this dosage included WBC 1300/mm3platelets 129,000/mm3, and hemoglobin 10.9 mg/dl. With dose escalation, hematologic toxicity was dose-limiting. Symptomatic cardiac toxicity was observed in one patient who had received maximum dose doxorubicin and radiotherapy. Median values for the cardiac ejection fraction during the full course of therapy for the entire group of patients were 0.62 (initial) and 0.60 (final).Idarubicin in intravenous form is an active drug in previously treated patients with unfavorable non-Hodgkin's lymphoma. Further studies employing idarubicin in non-Hodgkin's lymphoma should be considered. Cardiac function should be followed in trials utilizing anthracycline-type chemotherapeutic agents.

ISSN:1042-8194    

DOI:10.3109/10428199309149116

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:1042-8194    

DOI:10.3109/10428199309149117

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Between 1981 and 1986, 126 patients with advanced stage, large cell lymphoma were treated with MACOP-B chemotherapy. Their six-year failure-free and overall survival is 52% and 62% respectively. Eighty-eight patients aged 60 or less had an excellent six year overall survival of 68%. The outcome for various subsets of patients is analysed according to the number of adverse prognostic factors including age, stage, lactic dehydrogenase level and number of extra nodal sites.

ISSN:1042-8194    

DOI:10.3109/10428199309149118

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Management of early stages of Hodgkin's disease requires development of treatment programs that are nominally toxic, with a low likelihood of sterility and secondary malignancies, both associated with alkylating agents. Although patients with laparotomy-staged disease without B symptoms or large mediastinal masses have good results when treated with radiotherapy alone, patients with adverse features need chemotherapy for optimal disease-free survival results. MOPP and its variants have been studied extensively for adjuvant therapy of patients with early staged disease but are associated with the development of secondary malignancies, including acute leukemia and solid tumors. ABVD has been compared with MOPP in combination with radiation therapy for patients with stages IIB and IIIB. and ABVD is not associated with a high risk of acute leukemia; however, cardiac and pulmonary toxicities have been reported, and there may be long term complications following ABVD in combined modality programs.In 1988, we developed NOVP [mitoxantrone (NovantroneTM), vincristine, vinblastine, prednisone], designed as adjuvant chemotherapy to treat patients with clinically staged I-II Hodgkin's disease who had unfavorable features, including B symptoms, large mediastinal masses, and hilar lymph node involvement. We also included patients with peripheral masses≥10 cms and those with stage III disease. In the second phase of this study, we treated patients without adverse features, in order to avoid laparotomy. The treatment plan included three cycles of NOVP, followed by radiotherapy to the mantle and the abdomen, with fields depending upon disease presentation. Patients with large mediastinal masses or hilar involvement also received low dose lung radiotherapy. With a median follow-up of 18 months, 99 patients have received NOVP and radiotherapy. Ninety-seven percent entered CR and ten patients have experienced progressive disease.There are many reasonable choices of treatment for patients with Hodgkin's disease. However, those with adverse prognostic features need combined modality therapy, even when treatment includes prolonged intensive chemotherapy. Options for patients without large mediastinal masses or other adverse prognostic factors might still include staging by laparotomy followed by radiation therapy. However, treatment options including combined modality therapy and radiation therapy without laparotomy are also reasonable for these favorable groups, especially when chemotherapy regimens utilized are associated with low toxicity.

ISSN:1042-8194    

DOI:10.3109/10428199309149119

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:1042-8194    

DOI:10.3109/10428199309149120

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:1042-8194    

DOI:10.3109/10428199309149121

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Analysis of different ribonucleotide reductase inhibitors to modulate arabinosylcytosine (ara-C) metabolism suggested that pretreatment with arabinosyl-2-fluoroadenine (F-ara-A) significantly potentiated the rate of ara-CTP (5′-triphosphate of ara-C) accumulation in both quiescent lymphocytes (p = 0.046) and in cycling blasts (p = 0.017). In vitro incubations of freshly isolated leukemia cells from patients with chronic (n = 7) or acute (n = 5) leukemias with F-ara-A, increased the rate of ara-CTP accumulation by a median of 1.5 or 1.7-fold, respectively, when subsequently incubated with ara-C.The objective of the present investigation was to test the hypothesis that ara-C can be biochemically modulated during therapy of leukemias. To test the biochemical modulation of ara-C in the clinical setting, we designed two protocols to administer fludarabine (clinical formulation of F-ara-A) and ara-C in a pharmacologically directed sequence for patients with chronic lymphocytic leukemia (CLL) refractory to conventional fludarabine therapy or for patients with acute myelogenous leukemia (AML) in relapse. Comparison of ara-CTP pharmacokinetics demonstrated a significant increase in the area under concentration curve (AUC) of ara-CTP both in CLL (median 1.5-fold) and AML cells (median 1.8-fold) after fludarabine infusion. Analyses of different processes involved in the metabolism of ara-CTP indicated that the increase in AUC was due to potentiation of the rate of ara-CTP accumulation. These studies demonstrate that protocols designed on biochemical and pharmacological rationales modulate ara-C metabolism during therapies.

ISSN:1042-8194    

DOI:10.3109/10428199309149122

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

ISSN:1042-8194    

DOI:10.3109/10428199309149123

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor