High-dose chemotherapy with carboplatin, etoposide and ifosfamide followed by autologous stem cell rescue in patients with relapsed or refractory malignant lymphomas: a phase I/II study

Abstract

Summary:Advances in therapy of intermediate-or high-grade nonHodgkin's lymphomas (NHL) and Hodgkin's disease (HD) are one of the most important breakthroughs in oncology. Patients with relapsed or refractory non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) withUsing CHOP or newer second-and third-generation regimens, about 30-50% of patients with advanced NHL will recurrences after an anthracyclin-containing regimen only have a chance of cure of below 10% with convenachieve long-term disease-free survival (DFS). 1,2 Nevertheless, the outcome of the remaining 50-70% of patients who tional chemotherapy. In order to improve their prognosis, we started a phase I/II trial using high-dose therdo not achieve complete remission (CR) or who relapse is dismal. The 2-year disease-free survival with conventional apy comprising carboplatin, together with etoposide and ifosfamide (CEI), followed by autologous stem cell salvage chemotherapy regimens is less than 15% in most studies. [3][4][5] Therefore, several approaches have been made rescue (ASCR) as consolidation after salvage treatment. Since September 1990, 40 patients with intensively preto increase CR and DFS rates, most of them using highdose chemotherapy (HDT) regimens Ϯ total body treated advanced NHL (n = 24) or HD (n = 16) received one cycle of high-dose therapy (HDT) consisting of carirradiation (TBI) with autologous stem cell support. Widely used chemotherapeutic agents have been cyclophosphamboplatin 1500 mg/m 2 , ifosfamide 10 g/m 2 and etoposide in escalating doses from 1200 mg/m 2 to 2400 mg/m 2 folide, cytosine arabinoside, etoposide and BCNU. Combinations of three or four drugs in high dosages have regulowed by ASCR. Thirty-nine patients were assessable for toxicity and response. The following doses appeared larly shown substantial toxicitiy. [6][7][8] One possible way to improve results of HDT is with nonto be safe: carboplatin 1500 mg/m 2 , etoposide 2400 mg/m 2 and ifosfamide 10 g/m 2 . All patients developed crossresistant drugs which were not used during first-line and salvage treatment. They should have low non-hematograde 3 nausea and grade 3 or 4 mucositis. Granulocytopenic fever occurred in 100% with grade 4 infeclogic toxicity even in escalated doses. The topoisomerase II inhibitor etoposide has become one of the most effective tions in 15%. Mild transient kidney toxicity was noted in 36% and liver toxicity in 20% of patients. One toxic drugs for the treatment of NHL. Its synergism with alkylating agents and its limited non-hematologic toxicity makes death occurred (2.5%). Objective responses were obtained in 36 of 39 patients (92%) with complete it useful for combination in HDT. 9,10 Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of remissions (CR) in 24 patients (61.5%) and partial remissions (PR) in 12 (30.7%). Median observation antineoplastic activity producing favorable response rates, for example, in germ cell cancer, ovarian carcinoma, NHL time for surviving patients was 23.3 months (range 3.4-52.3). The ...

Perspectives on cancer therapy-induced mucosal injury

“…The incidence of oral and GI mucositis varied significantly among different treatment regimens and modalities (Table 4). 60–398 Most anthracycline‐based regimens were associated with rates of oral mucositis in the 1–10% range, except when regimens included 5‐FU. Included among these are the standard regimens for adjuvant therapy in patients with breast cancer (5‐FU, doxorubicin, and cyclophosphamide; doxorubicin and cyclophosphamide; or 5‐FU, epirubicin, and cyclophosphamide) as well as regimens for patients with non‐Hodgkin lymphomas, including cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).…”

Pediatric T- and NK-cell lymphomas: new biologic insights and treatment strategies

“…25, 26, 27 Modestly effective re-induction regimens include ICE (ifosfamide, carboplatin, and etoposide; 92% response rate seen in a 40 patient cohort containing 24 relapsed NHL) and DECAL (dexamethasone, etoposide, cisplatin, high-dose cytarabine and L -asparaginase; 50% response rate in a 58 patient NHL cohort, including 26 LBL cases). 28, 29 …”

“…28, 30 Relapses after allo-SCT were less common in a group of 204 LBL patients (most of whom had T-LBL), but higher transplant-related mortality was felt to offset any survival benefit. 31 However, this remains an open question.…”

Ten-year follow-up of pediatric patients with non-hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation

“…In adults, auto‐SCT has demonstrated a superior outcome when compared with chemotherapy alone for the treatment of relapsed NHL . The indications for auto‐SCT versus allo‐SCT are not clearly defined.…”