CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial

Abstract

SummaryBackgroundOutcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients.MethodsWe did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0–3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1–5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m2 on days 1, 8, and 15, cisplatin 100 mg/m2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1–5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18).FindingsBetween June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6–38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21–1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections.InterpretationThe number of patien...

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“…The optimal regimen for PTCL has yet to be determined, but most centers consider anthracycline-based regimens, mostly CHOP, for nodal PTCLs. 46 There are some questions if the addition of etoposide to CHOP could improve the outcome of patients with nodal PTCL, albeit at a higher hematological toxicity. 47 More intensive regimens have failed in improving responses in PTCL.…”

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“…[4] Due to their extreme toxicity, bifunctional alkylating agents were initially developed as chemical weapons and later,c ertain derivatives were recognized as having important chemotherapeutic activities. [5] Some of these agents are still widely used in the first line therapies of various lymphomas, [6] leukemias, [7] and solid tumors. [8] Thelow chemoselectivity of these drugs contributes to their undesirable side effects, [9] and their promiscuity makes it difficult to ascertain their exact mode of action.…”

Chidamide combined with cyclophosphamide, epirubicin, vindesine, prednisone, and etoposide (C-CHOEP) regimen is superior to the GDP-ML and CHOEP regimen for patients with newly diagnosed peripheral T-cell lymphoma

“…Gemcitabine-based regimens also failed to show advantage over standard CHOP regimen. In a phase 2 multicentre randomized trial, the CR rate of GEM-P regimen (gemcitabine, cisplatin, and methylprednisolone) was inferior to CHOP regimen (46% vs. 62%), with 2-year PFS rates of 38% versus 37%, respectively [9]. The above studies suggested that the past usage of cytotoxic chemotherapy at varying intensity was not su cient in the treatment of PTCL.…”

“…The addition of etoposide to CHOP (CHOEP) might improve response rate and event-free survival (EFS) for younger patients (aged ≤ 60 years) [7,8]. Non-anthracycline based regimens such as gemcitabine-based chemotherapy were explored in several studies for PTCL patients but still showed non-superior results compared to CHOP-like chemotherapy [9]. At our center, Zhang Y et al conducted a phase 2 study of GDP-ML regimen (combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase) in patients with newly diagnosed PTCLs, which showed an ORR of 55.4% and 2-year OS rate of 38.2% (registered with www.…”