Activity of 2-chlorodeoxyadenosine (cladribine) in 2-hour intravenous infusion in 94 previously treated patients with low grade non-hodgkin's lymphoma

Abstract

The purpose of our study was to determine the efficacy of 2-chlorodeoxyadenosine (2-CdA) administered in 2-hour intravenous infusions in previously treated patients with low grade non-Hodgkin's lymphoma (LGNHL). We treated 94 LGNHL patients with 2-CdA at a dosage of 0.12 mg/kg/24h in 2-hour intravenous infusion for 5 consecutive days. The treatment consisted of from 1 to 7 courses (median 3), repeated usually at monthly intervals. All patients were refractory to or relapsed after standard chemotherapy. Of these 94 patients 78 (83%) had clinical stage IV of the disease. Complete response (CR) was obtained in 12 (12.8%) and partial response (PR) in 36 (38.3%) giving an overall response rate of 51.1%. In 12 (12.8%) grade 4 thrombocytopenia with haemorrhagic diathesis was noted, grade 4 neutropenia was observed in 12 (12.8%) and infections complicated the course of treatment in 38 (40.4%) patients. 2-CdA treatment was the cause of death of 3 patients. The results of our study show that 2-CdA given in 2-hour infusions is an effective agent in advanced, heavily pretreated patients with LGNHL.

Beyond hairy cell: the activity of cladribine in other hematologic malignancies

“…27 These results were later reproduced in a trial where 80% of patients had a nonfollicular histology, mainly lymphoplasmacytic lymphoma (37%) or B-chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (29%). 28 Of 94 patients, 48 (51%) achieved a response and 12 (13%) had a CR. The median duration of response was 12 months for a CR and 6 months for a partial response.…”

“…[26][27][28][29][30][31][32][33][34][35][36] Cladribine demonstrated impressive activity with overall and CR rates of up to 72% and 38%, respectively. Follicular and nonfollicular histologies appeared to be equally responsive.…”

Rituximab combined with cladribine or with cladribine and cyclophosphamide in heavily pretreated patients with indolent lymphoproliferative disorders and mantle cell lymphoma

“…These results seem to be superior to those achieved earlier with 2-CdA alone, as reported by us and by other authors. [22][23][24] The RC/ RCC regimens also seem at least to be equally as efficient as 2-CdA in combination with cyclophosphamide and prednizone 25 and cyclophosphamide combined with either mitoxantrone 26 or etoposide. 27 Laurencet et al 25 reported a response in 88% patients, including 4 CRs among 19 patients who received 2-CdA combined with cyclophosphamide and prednisone.…”

Prolonged follow‐up after initial therapy with 2‐chlorodeoxyadenosine in patients with indolent non‐Hodgkin lymphoma

“…[18][19][20][21][22] Initial trials with 2-CdA established a maximal tolerated dose of 0.1 mg/kg per day as a continuous intravenous infusion over 7 days 23 ; however, because of its long half-life, bolus, subcutaneous, and oral regimens have been equally effective. 7,8,12,13,[15][16][17][24][25][26][27] Reported toxicities consist primarily of myelosuppression and bacterial and opportunistic infections, [4][5][6][7][8][9][10][11][12][13][14][15][16][17] with less frequent occurrences of autoimmune hemolytic anemia 28 and neurotoxicity. 29 Rare reports of an increased incidence of second malignancies or transformation to aggressive NHL have not been confirmed.…”

“…2-Chlorodeoxyadenosine (2-CdA) (cladribine, Leustatin) is a deoxyadenosine purine nucleoside analog that is toxic to both proliferating and resting lymphocytes (for review, see Tallman and Hakimian 1 ), with activity in chronic lymphocytic leukemia (CLL), 2,3 lowgrade NHL, [4][5][6][7][8][9][10][11][12][13][14][15][16][17] and hairy cell leukemia (HCL). [18][19][20][21][22] Initial trials with 2-CdA established a maximal tolerated dose of 0.1 mg/kg per day as a continuous intravenous infusion over 7 days 23 ; however, because of its long half-life, bolus, subcutaneous, and oral regimens have been equally effective.…”