ABSTRACT
PURPOSE: To determine whether modifying the standard regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) from full doses given every 3 weeks to one-third doses given weekly (chop) increases the received chemotherapy dose-intensity in elderly patients with advanced-stage intermediate-grade lymphoma. PATIENTS AND METHODS: Consenting patients, age > or = 65 years who had acceptable cardiac, renal, and liver function and an Eastern Cooperative Oncology Group (ECOG) performance status less than 4, were stratified by bone marrow and performance status and randomized to receive standard CHOP or weekly chop. Drug doses were attenuated or escalated according to a defined dose-modification schedule. The primary outcome was average relative received dose-intensity. Secondary outcomes included response, progression-free and overall survival, toxicity, and performance status. RESULTS: Nineteen patients were allocated to each group. No difference in received dose-intensity was seen. When dose-intensity was calculated for the first six cycles of therapy, average relative received dose-intensity was .92 with CHOP versus .89 with weekly chop (P = .5); when calculated for the first 18 weeks of therapy, values were .88 with CHOP versus .89 with weekly chop (P = .8). The complete response rate was 68% with CHOP versus 74% with weekly chop (P = .9). At 2 years, the progression-free survival rate was 57% with CHOP versus 46% with weekly chop (P = .16) and the survival rate was 74% with CHOP versus 51% with weekly chop (p = .05). More myelotoxicity was seen with CHOP. CONCLUSION: We conclude that CHOP can be given in sufficient doses to elderly patients and that weekly chop does not increase received dose-intensity. Progression-free and overall survival are unlikely to be superior with weekly chop, and may be worse. CHOP should remain the standard against which new therapies for elderly patients with intermediate-grade lymphoma are compared.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, Non-Hodgkin/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chi-Square Distribution , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Drug Administration Schedule , Female , Humans , Life Tables , Lymphoma, Non-Hodgkin/mortality , Male , Pilot Projects , Prednisone/administration & dosage , Prednisone/adverse effects , Remission Induction , Survival Rate , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
The purpose of this study was to determine the relationship between platinum-DNA adducts in leukemic cells and the success of remission induction therapy in adult patients with acute nonlymphocytic leukemia (ANLL). Freshly isolated cells from pre-treatment bone marrow aspirates of 14 patients were incubated with cisplatin in vitro and the amount of platinum bound to DNA was determined using a competitive ELISA procedure and an antibody directed against platinum-modified DNA. Platinum-DNA adduct levels discriminated well between complete remission (CR) and remission failure (RF) patients, treated with mitoxantrone, cytosine arabinoside +/- carboplatin.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/metabolism , DNA Adducts/analysis , Leukemia, Myeloid, Acute/pathology , Organoplatinum Compounds/analysis , Adolescent , Adult , Aged , Bone Marrow/metabolism , Bone Marrow/pathology , Cytarabine/administration & dosage , DNA Adducts/metabolism , Female , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Male , Middle Aged , Mitoxantrone/administration & dosage , Organoplatinum Compounds/metabolism , Predictive Value of Tests , Recurrence , Remission InductionABSTRACT
Eleven patients with acute non-lymphocytic leukemia and persistent leukemia on a bone marrow done 6 days after the start of standard induction chemotherapy with daunorubicin and cytosine arabinoside were given augmentation chemotherapy with carboplatin as a continuous intravenous infusion over 3 days. Nine of the 11 patients (82%) entered complete remission. The hematologic and non-hematologic toxicities encountered by these patients were similar to those seen after conventional therapy alone with the exception of peripheral neuropathy in one patient. Of the two induction failures, one patient died of treatment-related toxicity and one patient had resistant leukemia.
Subject(s)
Carboplatin/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/pathology , Carboplatin/adverse effects , Humans , Kidney Diseases/chemically induced , Leukemia, Myeloid, Acute/pathology , Middle AgedABSTRACT
Of patients referred to a geriatric service, 66 were identified who were clearly anemic (hemoglobin less than 12 g in men, less than 11 g in women) but whose cause of anemia was not readily identifiable by noninvasive measures. The difficulty in distinguishing iron deficiency from chronic disease as a cause of anemia by noninvasive means (serum iron, total iron binding capacity, transferrin saturation ratio, and serum ferritin), is highlighted by the poor power of these investigations when compared with bone marrow iron stores. A transferrin saturation ratio of less than 11% and a serum ferritin of less than 45 pg/L serve better than currently accepted values to identify iron deficiency in this population.
