ABSTRACT
BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.
Subject(s)
Ki-1 Antigen , Lymphoma, T-Cell, Peripheral , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brentuximab Vedotin , Humans , Ki-1 Antigen/metabolism , Ki-1 Antigen/therapeutic use , Lymphoma, T-Cell, Peripheral/drug therapy , Vincristine/adverse effectsABSTRACT
Peripheral T-cell lymphomas (PTCLs) are an uncommon group of lymphoproliferative disorders accounting for approximately 10-15 % of all non-Hodgkin lymphomas (NHL) in Western countries. Although PTCLs are associated with poor prognosis, outcomes vary with disease subtype. The standard of care has been anthracycline-based induction combination chemotherapy, however, with the exception of low-risk ALK-positive anaplastic large cell lymphoma, relapse rates are high. Therefore, consolidation with autologous stem cell transplantation is usually recommended for patients deemed candidates, and with aggressive subtypes. In recent years, a number of novel agents including pralatrexate, histone deacetylase inhibitors, immunotoxins, proteasome inhibitors, aurora kinase inhibitors and the CD30 antibody-drug conjugate brentuximab vedotin, have shown promise in the treatment of PTCLs. Studies are underway to explore the activity of these newer agents used in the frontline setting.
Subject(s)
Lymphoma, T-Cell, Peripheral/diagnosis , Lymphoma, T-Cell, Peripheral/therapy , Aminopterin/analogs & derivatives , Aminopterin/therapeutic use , Antineoplastic Agents/therapeutic use , Brentuximab Vedotin , Diphtheria Toxin/therapeutic use , Histone Deacetylase Inhibitors/therapeutic use , Humans , Immunoconjugates/therapeutic use , Interleukin-2/therapeutic use , Lymphoma, T-Cell, Peripheral/pathology , Molecular Targeted Therapy , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Stem Cell TransplantationABSTRACT
BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), the value of (18)fluoro-deoxyglucose positron emission tomography (FDG-PET) scans for assessing prognosis and response to treatment remains unclear. The utility of FDG-PET, in addition to conventional radiology, was examined as a planned exploratory end point in the pivotal phase 2 trial of romidepsin for the treatment of relapsed/refractory PTCL. PATIENTS AND METHODS: Patients received romidepsin at a dose of 14 mg/m(2) on days 1, 8, and 15 of 28-day cycles. The primary end point was the rate of confirmed/unconfirmed complete response (CR/CRu) as assessed by International Workshop Criteria (IWC) using conventional radiology. For the exploratory PET end point, patients with at least baseline FDG-PET scans were assessed by IWC + PET criteria. RESULTS: Of 130 patients, 110 had baseline FDG-PET scans, and 105 were PET positive at baseline. The use of IWC + PET criteria increased the objective response rate to 30% compared with 26% by conventional radiology. Durations of response were well differentiated by both conventional radiology response criteria [CR/CRu versus partial response (PR), P = 0.0001] and PET status (negative versus positive, P < 0.0001). Patients who achieved CR/CRu had prolonged progression-free survival (PFS, median 25.9 months) compared with other response groups (P = 0.0007). Patients who achieved PR or stable disease (SD) had similar PFS (median 7.2 and 6.3 months, respectively, P = 0.6427). When grouping PR and SD patients by PET status, patients with PET-negative versus PET-positive disease had a median PFS of 18.2 versus 7.1 months (P = 0.0923). CONCLUSIONS: Routine use of FDG-PET does not obviate conventional staging, but may aid in determining prognosis and refine response assessments for patients with PTCL, particularly for those who do not achieve CR/CRu by conventional staging. The optimal way to incorporate FDG-PET scans for patients with PTCL remains to be determined. TRIAL REGISTRATION: NCT00426764.
Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Depsipeptides/therapeutic use , Drug Resistance, Neoplasm/drug effects , Fluorodeoxyglucose F18/pharmacokinetics , Lymphoma, T-Cell, Peripheral/diagnostic imaging , Positron-Emission Tomography/statistics & numerical data , Follow-Up Studies , Humans , Lymphoma, T-Cell, Peripheral/drug therapy , Lymphoma, T-Cell, Peripheral/mortality , Lymphoma, T-Cell, Peripheral/pathology , Neoplasm Staging , Prognosis , Prospective Studies , Radiopharmaceuticals/pharmacokinetics , Remission Induction , Survival Rate , Tissue DistributionABSTRACT
Lenalidomide-rituximab therapy is effective in grade 1-2 follicular and mantle cell lymphoma, but its efficacy in diffuse large B-cell lymphoma (DLBCL), transformed large cell lymphoma (TL) and grade 3 follicular lymphoma (FLG3) is unknown. In this phase II trial, 45 patients with relapsed or refractory DLBCL (n=32), TL (n=9) or FLG3 (n=4) who had received 1-4 prior lines of treatment were given 20 mg oral lenalidomide on days 1-21 of each 28-day cycle, and intravenous rituximab (375 mg/m(2)) weekly during cycle 1. Grade 3/4 hematological toxicities included neutropenia (53%), lymphopenia (40%), thrombocytopenia (33%), leukopenia (27%) and anemia (18%), with a median follow-up time of 29.1 months (range 14.7-52.0 months). Overall response (OR) rate was 33%; median response duration was 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were 3.7 and 10.7 months, respectively. Nine of the 15 responding patients (three partial response (PR), six complete response (CR)) proceeded with stem cell transplantation (SCT) and were censored at the time of transplantation. When data were analyzed without censoring, median PFS remained 3.7 months and response duration increased to 30.9 months. Rituximab plus oral lenalidomide is well tolerated and effective for patients with relapsed/refractory DLBCL and TL. SCT after lenalidomide-rituximab is associated with prolonged response duration.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Administration, Oral , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Disease Progression , Female , Hematopoietic Stem Cell Transplantation , Humans , Lenalidomide , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/mortality , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Recurrence , Rituximab , Thalidomide/administration & dosage , Thalidomide/analogs & derivatives , Tomography, X-Ray Computed , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults. PATIENTS AND METHODS: We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS. RESULTS: Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis. CONCLUSIONS: Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.
Subject(s)
Gout Suppressants/administration & dosage , Tumor Lysis Syndrome/prevention & control , Urate Oxidase/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Female , Gout Suppressants/therapeutic use , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Middle Aged , Risk Factors , Treatment Outcome , Tumor Lysis Syndrome/etiology , Urate Oxidase/therapeutic use , Uric Acid/bloodABSTRACT
BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare peripheral T-cell lymphoma; treatment with standard anthracycline-containing chemotherapy regimens has been disappointing, and an optimal treatment strategy for this patient population has not yet been determined. METHODS: We identified 15 cases of pathologically confirmed HSTCL in the institution's database. Clinical characteristics and treatment results were reviewed. RESULTS: Complete responses (CRs) were achieved in 7 of 14 patients who received chemotherapy. Achievement of CR was followed by hematopoietic stem-cell transplantation in three patients. Median duration of CR was 8 months (range 2 to 32+ months) with four patients currently alive and in CR at 5, 8, 12, and 32 months, respectively. Median overall survival (OS) was 11 months (range 2 to 36+ months). Patients who achieved a CR had a median OS of 13 months, compared with 7.5 months in patients who did not achieve a CR. Risk factors associated with worse outcome included male gender, failure to achieve a CR, history of immunocompromise, and absence of a T-cell receptor gene rearrangement in the gamma chain. CONCLUSION: A better understanding of the pathophysiology of HSTCL and new therapeutic strategies are needed.
Subject(s)
Lymphoma, T-Cell, Peripheral/pathology , Lymphoma, T-Cell, Peripheral/therapy , Adult , Female , Hematopoietic Stem Cell Transplantation , Humans , Lymphoma, T-Cell, Peripheral/diagnosis , Lymphoma, T-Cell, Peripheral/drug therapy , Male , Middle Aged , Survival Analysis , Young AdultABSTRACT
BACKGROUND: To determine the efficacy and side-effects of (90)Y ibritumomab tiuxetan (Zevalin) as front-line treatment in patients with early-stage extranodal indolent lymphoma of the ocular adnexa (orbit, conjunctiva, or eyelid). PATIENTS AND METHODS: From August 2004 to November 2007, 12 patients with stages I-E extranodal indolent lymphoma of the ocular adnexa were enrolled in a prospective trial of rituximab followed by (90)Y ibritumomab tiuxetan (Zevalin therapeutic regimen). For each patient, clinical examinations and imaging studies were used to document response to therapy using the The International Working Group response criteria. All patients had (111)In ibritumomab tixuetan imaging to confirm expected biodistribution before (90)Y-Zevalin therapy; in addition, three patients had an optional single photon emission computed tomography-computed tomography scan to estimate the absorbed radiation dose to the orbital and ocular tissues. RESULTS: The study included seven women and five men. The median age was 60 years (range 22-79). Nine patients had mucosa-associated lymphoid tissue lymphoma of conjunctiva or orbit; three patients had grades 1-2 follicular lymphoma of orbit. One patient who had been deemed stage I-E initially was found to have another lesion in her deltoid muscle on positron emission tomography 2 weeks after enrollment. She was kept on trial although her disease was reclassified as stage IV due to this single additional (biopsy-proven) site. Ten patients had a complete response and two partial response (PR) within 3 months of treatment. One patient had a recurrence in the upper eyelid 6 months after an initial PR; he then received 30 Gy of external-beam radiotherapy (EBRT). His disease later progressed again in the orbit and he is currently being considered for other treatments. A second patient who attained a PR has remained stable with no progression 12 months after treatment. With a median follow-up time of 20 months (range 6-44 months), there were no cases of distant (extraorbital) relapse. All 12 patients experienced grade I or II transient pancytopenia during the first 3 months after enrollment in the trial. There were no episodes of grade III or IV myelosuppression. The estimated absorbed radiation dose to the orbital soft tissues was <3 Gy, 10 times lower than that with EBRT. CONCLUSIONS: Rituximab followed by (90)Y ibritumomab tiuxetan is an effective and safe front-line treatment for early-stage extranodal indolent B-cell lymphoma of the ocular adnexa.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Eye Neoplasms/drug therapy , Lymphoma, B-Cell, Marginal Zone/drug therapy , Radioimmunotherapy , Yttrium Radioisotopes/therapeutic use , Adult , Aged , Antibodies, Monoclonal/adverse effects , Eye Neoplasms/pathology , Female , Humans , Lymphoma, B-Cell, Marginal Zone/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Prospective Studies , Yttrium Radioisotopes/adverse effectsABSTRACT
BACKGROUND: The benefit of adding rituximab to anthracycline-based therapy for follicular lymphoma grade 3 has not been studied. PATIENTS AND METHODS: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center. Response rate, failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to CHOP-only-treated patients was made. RESULTS: The International Prognostic Index (IPI) distribution was 47% low, 36% low intermediate, 13% high intermediate, and 4% high risk. The complete response rate was 96%. Forty-four of 45 patients are still alive. Median follow-up for the alive patients is 3.5 years. The 3-year FFS rate according to the IPI was 80% [95% confidence interval (CI) 64% to 100%] in low, 81% in low intermediate (95% CI 64% to 100%), and 50% (95% CI 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI 58% to 87%) compared with 44% (95% CI 36% to 55%) with P value of 0.019, and 5-year OS, 98% (95% CI 93% to 100%) compared with 75% (95% CI 67% to 84%) with P value of 0.0034. CONCLUSION: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor-risk patients continue to demonstrate a high rate of failure despite the use of rituximab.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/mortality , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived , Cohort Studies , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prednisone/administration & dosage , Proportional Hazards Models , Rituximab , Salvage Therapy , Survival Rate , Vincristine/administration & dosageABSTRACT
A total of 40 patients with relapsed/refractory Hodgkin's disease (HD) underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) from an HLA-identical sibling (n=20) or a matched unrelated donor (n=20). The median age was 31 years (range 18-58). Disease status at allo-SCT was refractory relapse (n=14) or sensitive relapse (n=26). The conditioning regimens were fludarabine-cyclophosphamide+/-antithymocyte globulin (n=14), a less intensive regimen, and fludarabine-melphalan (FM) (n=26), a more intensive one. The two groups had similar prognostic factors. The median time to neutrophil recovery (ie absolute neutrophil count >/=500/microl) was 12 days (range 10-24). The median time to platelet recovery (ie platelet count >/=20 000/microl) was 17 days (range 7-132). Day 100 and cumulative (18-month) transplant-related mortalities (TRMs) were 5 and 22%. Twenty-four patients (60%) are alive (14 in complete remission or complete remission, unconfirmed/uncertain) with a median follow-up of 13 months (4-78). In all, 16 patients expired (TRM n=8, disease progression n=8). FM patients had better overall survival (73 vs 39% at 18 months; P=0.03), and a trend towards better progression-free survival (37 vs 21% at 18 months; P=0.2). RIC allo-SCT is feasible in relapsed/refractory HD patients with a low TRM. The intensity of the preparative regimen affects survival.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hodgkin Disease/therapy , Transplantation Conditioning , Adolescent , Adult , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/mortality , Hodgkin Disease/mortality , Humans , Leukocyte Transfusion , Male , Middle Aged , Transplantation, HomologousABSTRACT
CD26/Dipeptidyl Peptidase IV (DPPIV) is a 110-kDa glycoprotein that is expressed on numerous cell types and has multiple biological functions. A key facet of CD26/DPPIV biology is its enzymatic activity and its physical and functional interaction with other molecules. The substrates of CD26/DPPIV are proline-containing peptides and include growth factors, chemokines, neuropeptides, and vasoactive peptides. DPPIV plays an important role in immune regulation, signal transduction, and apoptosis. Furthermore, CD26 appears to play an important role in tumor progression. In the present review, we summarize key aspects of CD26/DPPIV involvement in tumor biology and its potential role in cancer development and behavior.
Subject(s)
Dipeptidyl Peptidase 4/physiology , Neoplasms/enzymology , Neoplasms/immunology , Humans , Lymphoma, T-Cell/enzymology , Lymphoma, T-Cell/etiology , Lymphoma, T-Cell/immunology , Neoplasm Metastasis , Neoplasms/etiology , Prognosis , Signal Transduction , T-Lymphocytes/enzymology , T-Lymphocytes/immunologyABSTRACT
Because irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a broad spectrum of antitumor clinical activity, we investigated its activity in relapsed or refractory non-Hodgkin's lymphomas (NHLs). Irinotecan at 300 mg/m2 i.v. was administered every 21 days with intensive loperamide management of diarrhea. Responders received up to six treatment cycles. Of 44 registered patients, 32 are evaluable for response. Seventeen patients had received one previous regimen, and 15 patients had received two. Disease was refractory to the regimen preceding irinotecan in 12 patients. At baseline, serum lactate dehydrogenase levels were high in 47% (14/30), and beta-2-microglobulin levels were higher than 3.0 mg/L in 29% (8/28) of patients. Responses were seen in 12 of 32 (38%) patients (95% confidence interval [CI] = 21%-56%). Response rates were 43% for seven indolent (95% CI = 10%-82%), 0% for three mantle cell (95% CI = 0%-71%), 44% for 18 relapsed aggressive (95% CI = 22%-69%), and 20% for five refractory aggressive NHLs (95% CI = 1%-72%). Grade 3/4 toxicities included myelosuppression, neutropenic fever, and diarrhea. Irinotecan appears active and relatively well tolerated in patients with relapsed aggressive or indolent NHL. Accrual to this study is continuing for better determination of response rates in all histologic subtypes of NHL.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Camptothecin/analogs & derivatives , Camptothecin/administration & dosage , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/pathology , Adult , Aged , Antineoplastic Agents, Phytogenic/adverse effects , Biopsy, Needle , Camptothecin/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Irinotecan , Lymphoma, Non-Hodgkin/mortality , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Patient Selection , Recurrence , Severity of Illness Index , Survival Analysis , Treatment OutcomeABSTRACT
PURPOSE: Severe diarrhea can represent a dose-limiting toxicity with the use of CPT-11. Conventional therapy is ineffective in some patients and is also limited by patient compliance. We report our observation on the effectiveness of octreotide acetate in the treatment of CPT-11-induced diarrhea refractory to opioids. PATIENTS AND METHODS: We describe 4 patients with metastatic gastrointestinal tumors who developed severe diarrhea following treatment with CPT-11 (65-125 mg/m2/weekly for 4 weeks every 6 weeks). Diarrhea was refractory to treatment with loperamide and diphenoxylate and was treated with octreotide acetate. RESULTS: Complete resolution of diarrhea was observed within 2-4 days of octreotide acetate treatment. Three patients responded to SC octreotide given every 8 hours and the 4th patient to octreotide given by continuous s.c. infusion. CONCLUSIONS: Our preliminary observation suggests value of octreotide in the control of CPT-11 induced refractory diarrhea. Prospective studies are warranted.
Subject(s)
Antidiarrheals/therapeutic use , Antineoplastic Agents, Phytogenic/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/adverse effects , Diarrhea/drug therapy , Octreotide/therapeutic use , Adult , Aged , Diarrhea/chemically induced , Female , Gastrointestinal Neoplasms/drug therapy , Humans , Irinotecan , Male , Middle Aged , Treatment OutcomeABSTRACT
Irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a broad spectrum of antitumor clinical activity. Various schedules and doses have been studied, and major complications were delayed diarrhea and myelosuppression. We explored the activity of irinotecan in patients with relapsed or refractory non-Hodgkin's lymphoma, using a 3-week schedule of administration. Eligible patients had histologically proven relapse, had received no more than two previous regimens, were > or = 15 years and < or = 75 years old, had normal renal function, neutrophil count > 1,500/microL, platelet count > 100,000/microL, and no human immunodeficiency virus infection or central nervous system involvement. Patients were treated with irinotecan 300 mg/m2 i.v. every 21 days with intensive loperamide management of diarrhea. Responders received up to six treatment cycles. Of 25 patients registered so far, 22 are evaluable for response. The median age was 67 years (range: 25 to 74 years) and 11 were male. The median number of previous regimens was 2 (range: 1 to 4 regimens), and 16 patients had disease that was refractory to their last regimen. Serum lactate dehydrogenase level was high in 75%, and beta2-microglobulin was > 3.0 mg/L in 26% of patients. Responses were seen in 8 of 22 (36%) patients with non-Hodgkin's lymphoma. Response rates were 40% for indolent, 0% for mantle cell, 45% for relapsed aggressive, and 33% for refractory aggressive lymphomas. Grade 3/4 toxicities included myelosuppression, neutropenic fever, and delayed diarrhea. Irinotecan appears active and relatively well tolerated in patients with relapsed aggressive non-Hodgkin's lymphoma. Accrual to this study is continuing for better determination of the response rate in all histologic subtypes of non-Hodgkin's lymphoma.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Enzyme Inhibitors/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Topoisomerase I Inhibitors , Adult , Aged , Antineoplastic Agents, Phytogenic/administration & dosage , Camptothecin/administration & dosage , Drug Administration Schedule , Female , Humans , Irinotecan , Male , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: In the current study, the authors analyzed prognostic factors in patients with aggressive lymphoma treated with a chemotherapy regimen comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without radiotherapy. METHODS: Between September 1988 and December 1996, 294 patients with newly diagnosed, clinical Ann Arbor Stage I-IV, aggressive lymphoma were enrolled on 2 protocols at The University of Texas M. D. Anderson Cancer Center. Patients on these studies had a relatively favorable prognosis; 100% had M. D. Anderson tumor scores
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Lymphoma/drug therapy , Lymphoma/pathology , Lymphoma/radiotherapy , Prednisone/administration & dosage , Vincristine/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Disease-Free Survival , Follow-Up Studies , Humans , L-Lactate Dehydrogenase/blood , Middle Aged , Multivariate Analysis , Neoplasm Staging/methods , PrognosisABSTRACT
We report the frequency, presenting characteristics, progression-free survival, event-free survival, overall survival and AIDS-free survival of patients with previously untreated Hodgkin's disease (HD) in the setting of infection by human immunodeficiency virus (HIV). To accomplish this we retrospectively reviewed all untreated patients presenting to the University of Texas M.D. Anderson Cancer Center between July 1985 and August 1999 with HD and HIV infection. All available records were reviewed to determine presentation, clinical characteristics, treatment outcome, progression-free survival and overall survival. We identified 887 patients with HD and 3,500 with Non-Hodgkin's Lymphoma (NHL). The ratio of NHL to HD in HIV-negative versus HIV-positive patients was 3.9 versus 6.9, respectively. There were 14 HIV-positive patients with HD and 97 with NHL. The median age of the HIV-positive HD patients was 33 years, and 13 were male. Three patients had Acquired Immune Deficiency syndrome (AIDS) at the time of HD diagnosis, and seven had B-symptoms. Ann Arbor stage was I in one, II in three, III in four and IV in six patients. Mixed cellularity histology was seen in eight, bone marrow involvement in five and extranodal disease in seven patients. Four patients had elevated serum lactate dehydrogenase, three low serum albumin, and nine elevated serum beta2-microglobulin, The median CD4 count was 160/microl. Eleven patients received ABVD or equivalent regimens, followed by radiotherapy in five. One patient was treated with COPP and radiotherapy, one with NOVP and radiotherapy and one only with radiotherapy. All patients received some antiretroviral therapy, but it was variable over the years. With a median follow-up of 64 months for survivors, the projected 5-year progression-free survival was 64%, event-free survival 45%, overall survival 54% and AIDS-free survival 45%. Six patients died of complications arising from HIV infection, including one patient who had preexisting AIDS at HD presentation. Two patients died of HD, without developing other conditions diagnostic of AIDS. We conclude that in our referral patient population HIV infection is associated with preferential development of NHL rather than HD, which appears curable with standard treatment regimens. Since HIV-related deaths exceed those caused by HD, future investigation should focus on integration of chemotherapy and highly active antiretroviral therapy.