Source: DGNews  |  Posted 6 years ago

By Chris Berrie

LUGANO, SWITZERLAND -- June 9, 2005 -- Researchers have found a less invasive regimen for treatment of elderly patients with aggressive non-Hodgkin's lymphoma (NHL) than the current cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) regimen.

A 12-week treatment with prednisolone, mitoxantrone cyclophosphamide, etoposide, bleomycin, and vincristine (PMitCEBO) is a safe and efficacious alternative to 18-24 weeks of CHOP in these patients, according to a prospective, multicentre, randomised, phase 3 trial. The outcomes were not affected by the randomised prophylactic use of granulocyte colony-stimulating factor (G-CSF).

Investigator Cathy Burton, MD, clinical research fellow, Lymphoma Trials Office, Clinical Trials Centre, University College London, London, United Kingdom, presented the findings here on June 8[^]th[] at the 9[^]th[] International Conference on Malignant Lymphoma (ICML).

The median age for presentation of aggressive NHL is in excess of 60 years, with 45% over 65. These patients specifically need a regimen that decreases the rate of toxic death seen with the standard CHOP regimen.

Dr. Burton and colleagues therefore compared the efficacy and safety of the less aggressive PMitCEBO regimen against the current standard CHOP, with or without G-CSF, to allow an increased dose intensity and potentially improve overall survival. The study endpoints were overall and failure-free survival, complete response rate, toxic death rate, and toxicity.

Inclusion criteria were age over 60 years, and newly presenting aggressive NHL (bulky stage IA; stages IB to IV disease). Among the exclusion criteria were lymphoblastic and Burkitt's lymphoma, previous malignancy, and central nervous system involvement.

From 1997 to 2003, 784 patients were enrolled (median age, 70 years; range 60-89 years; male, 52%). Patient characteristics were balanced between the CHOP (n = 195), CHOP + G-CSF (n = 192), PMitCEBO (n = 202), and PMitCEBO + G-CSF (n = 195) arms, with disease statuses of: B symptoms, 54%; raised LDL, 62%; World Health Organisation performance status 0/1/2/3/4, 32%/40%/20%/6%/2%, age-adjusted international prognostic index (IPI) scores 0/1/2/3, 16%/30%/37%/17%.

The CHOP regimen was repeated 3 times weekly for 6 to 8 cycles consisted of day-1 dosing of the IV combination of 750 mg/m[^]2[] cyclophosphamide, 50 mg/m[^]2[] adriamycin, and 1.4 mg/m[^]2[] (maximum 2 mg) vincristine; with 100 mg oral prednisone on days 1 to 5.

The PMitCEBO regimen was repeated every 2 weeks for 6 cycles and included IV administration on day 1 of 7 mg/m[^]2[] mitoxantrone, 300 mg/m[^]2[] cyclophosphamide, 150 mg/m[^]2[] etoposide IV infused over 1 hour, as well as IV administration on day 8 of vincristine at a dose of 1.4 mg/m[^]2[] (maximum 2 mg) with 10 mg/m[^]2[] bleomycin IV bolus. This was also combined with prednisone 50 mg/day on week 1 to 4; the same prednisone dose was then given on alternate days from week 5 to the end of the treatment.

All patients also received 480 mg septrin BD, 3 times per week from week 1 to 2 weeks after treatment end, and 300 mg allopurinol OD on weeks 1 to 3. The G-CSF (lenograstim) randomisation was given on days 8 and 14 in the CHOP group, and on days 6 and 12 in the PMitCEBO group.

Results show that although G-CSF reduced the incidence of haematological toxicity in the PMitCEBO group, the CHOP arm had significantly lower grade 3 and 4 leucopaenia (P <.001). Rates of grade 2 to 4 infections, grade 2 to 4 nausea and vomiting, and alopecia were greater in the CHOP arm, but there was more neuropathy in the PMitCEBO arm.

With response rates assessed regularly (CHOP, 2, 4, 6 courses; PMitCEBO, 4, 8, 12 weeks), no significant differences in overall response rates were seen. However, the complete response rate with CHOP was significantly (P =.035) higher than for PMitCEBO.

At a media follow-up of 44 months, there were no statistical differences between the 4 arms in rates of failure-free, progression-free, and overall survival, with a 3-year overall survival of 47% for all patients. Although G-CSF had no influence on these parameters, subgroup analysis indicated that it significantly improved progression-free survival for the CHOP patients (P =.05).

Dr. Burton concluded that this less aggressive PMitCEBO regimen is as efficacious as CHOP, while being equivalently tolerated.

As this trial was conducted before the era of rituximab use in this setting, Dr Burton stressed that, "It has been shown that this regimen can be used with rituximab, and so the combination of rituximab and PMitCEBO should prove to be a safe and efficacious regimen for elderly patients with aggressive NHL."

[Study title: A Phase III Trial Comparing CHOP to PMitCEBO With or Without G-CSF in Patients Aged 60 Plus With Aggressive Non-Hodgkin's Lymphoma. Abstract 226]