Chemotherapy regimens devised for elderly patients with intermediate-high grade NHL are a matter of discussion. The aim is to reduce general toxicity without loosing an antilymphoma effect. The most important limiting factor of chemotherapy is myelotoxicity; for this reason the use of growth factor may be useful in these patients.
From November '91 to November '92, 67 pts older than 65 years with intermediate-and high-grade advanced-stage NHL were treated with the P-VEBEC regimen, an original scheme with epirubicin 50 mg/m2, cyclophosphamide 350 mg/m2 and etoposide 100 mg/m2 on weeks 1, 3, 5, 7; vinblastine 5 mg/m2 and bleomycin 5 mg/m2 on weeks 2, 4, 6, 8, prednisone 50 mg/m2/day p. os in the first 2 weeks and thereafter every other day. Twenty-eight pts received r-GSF 5 micrograms/kg/day throughout the treatment starting on day 2 of every week for 4 consecutive days. Their median age was 71 years (65-80), 31 pts were male and 36 female, histology according W.F. was D 6; E 17; F 16; G 19; H 9. Twenty-five percent of pts had B symptoms, 35% had bulky disease, 41% LDH level > normal, 44% stage IV and 26% had B.M. involvement.
C.R. was achieved by 66% of pts. Adverse prognostic factors for CR were E histology, stage IV, bone marrow infiltration and LDH above normal. Severe toxicity was never recorded, no toxic death was observed. With a median follow-up of 24 months OS, DFS and EFS were 55%, 52%, and 33%, respectively. EFS was influenced by stage, BM involvement and level of LDH. The relative dose intensity (RDI) was calculated by the method of Hryniuk and Bush. Patients who received rG-CSF had a significantly higher median RDI (94% vs 79%) and lower myelotoxicity (neutrophil nadir < 500 18% vs 56%). The rate of CR was influenced by RDI > 80% (89% vs 56%). EFS was also better in pts who received a RDI higher than 80% (50% vs 18% p = 0.05).
P-VEBEC is a feasible cycle in elderly patients; the use of rG-CSF improves RDI. In patients with adverse prognostic factors (BM involvement, poor performance status) a RDI > 0.80 could play a role in improving the outcome.
"Both the PMitCEBO and CHOP regimens result in considerable myelosuppression in the elderly population and the value of using granulocyte colony-stimulating factor (G-CSF) to mitigate against the chemotherapy induced neutropenia was also explored. Previous studies in lymphoma have suggested that the use of G- CSF results in less granulocyte suppression, less infection and hospitalisation, possibly allowing a higher dose intensity with improved response rates and with significant economic benefits (Pettengell et al, 1992; Gerhartz et al, 1993; Bertini et al, 1994; Zagonel et al, 1994; Niitsu and Umeda, 1995; Silvestri et al, 1995). Few previous studies have been adequately powered, however, to evaluate the impact of G-CSF use on survival. "
[Show abstract][Hide abstract] ABSTRACT: The management of older patients with aggressive non-Hodgkin's lymphoma presents a challenge to the physician. Age is a poor prognostic indicator, due to reduced ability to tolerate and maintain dose-intensive chemotherapy. Generally, older patients demonstrate a lower response rate, reduced survival and increased toxicity, although the majority of large randomised trials exclude older patients. This randomised trial was conducted in patients 60 years or over to compare CHOP (cyclophosphamide 750 mg m(-2), doxorubicin 50 mg m(-2), vincristine 1.4 mg m(-2), prednisolone 100 mg) with PMitCEBO (mitoxantrone 7 mg m(-2), cyclophosphamide 300 mg m(-2), etoposide 150 mg m(-2), vincristine 1.4 mg m(-2), bleomycin 10 mg m(-2) and prednisolone 50 mg). Due to the myelosuppressive nature of these regimens, patients were also randomised to the addition of G-CSF. The formal results of this trial with long-term follow-up are now reported. Data were analysed to assess efficacy and toxicity. Overall response rate was 84% in the CHOP arm and 83% in the PMitCEBO arm, with overall response rates of 83% for the use of G-CSF and 84% for no G-CSF. At median 44 months follow-up, there was no significant difference in failure-free, progression-free or overall survival between the CHOP and PMitCEBO arms. At 3 years, the actuarial failure-free survival was 44% in CHOP recipients and 42% in PMitCEBO recipients and the 3-year actuarial overall survival was 46% and 45% respectively. There was no significant difference in the failure-free, progression-free or overall survival with the addition of G-CSF.
British Journal of Cancer 04/2006; 94(6):806-13. DOI:10.1038/sj.bjc.6602975 · 4.84 Impact Factor
"TABLE 1 Grade 4 Neutropenia, Febrile Neutropenia, and Treatment-Related Mortality in Older Patients with Large Cell NHL Who were Treated with CHOP and CHOP-Like Regimens Study Regimen (no. of patients) Patient age (yrs) Patients with Grade 4 neutropenia Febrile neutropenia Treatment- related mortality Zinzani et al., 1999 21 VNCOP-B (350; CSF used in 71%) Ն 60 29% NR 1% Sonneveld et al., 1995 17 CHOP (72) Ն 60 NR NR 15% CNOP (76) Ն 60 NR NR 14% Gomez et al., 1998 15 CHOP (267) 60–69 (n ϭ 126) NR NR 12% 70–79 (n ϭ 115) NR NR 13% 80–94 (n ϭ 26) NR NR 19% Tirelli et al., 1998 18 VMP (60) Ն 70 50% NR 5% CHOP (60) Ն 70 47% NR 2% Bastion et al., 1997 11 CVP (219) Ն 70 4% a,b NR 12% CTVP (231) Ն 70 15% a,b NR 15% O'Reilly et al., 1993 16 P/DOCE (63) Ն 65 50% b 20% c 8% Björkholm et al., 1999 13 CHOP (104) or Ն 60 91% 47% NR CNOP (125) Bertini et al., 1994 12 P-VEBEC (39) 65–80 56% b 10% c 0% Coiffier et al., 2002 14 CHOP (197) 60–80 NR 25% c NR CHOP ϩ rituximab (202) NR 14% c NR "
[Show abstract][Hide abstract] ABSTRACT: Strategies for treating cancer are evolving to address the growing number of elderly patients with cancer. Older patients have highly variable physiologic ages, and their treatment should be individualized for optimal outcomes. Treatment paradigms should also take into account the diversity of patients' life expectancy, functional reserve, social support, and personal preference. A Comprehensive Geriatric Assessment (CGA) is a useful tool for estimating life expectancy and tolerance of treatment and for identifying reversible factors that may interfere with cancer treatment, including depression, malnutrition, anemia, neutropenia, and lack of caregiver support. Adopting a common language to describe older patients may facilitate the design and analysis of studies to determine effective drugs and care strategies for them. Information from a CGA can guide the prescription of potentially curative therapy, determine the best use of supportive care agents, and help identify frail patients for whom palliative care is the best option. There is evidence in a number of settings that the routine use of a CGA has a positive effect on health outcomes by reducing hospitalizations, preserving functional independence, and preventing geriatric syndromes. Guidelines for supportive care are also important in treating elderly patients with cancer. Pain, caused by cancer or its treatment, is prevalent, and guidelines for its assessment and treatment should be implemented to improve quality of life. Toxicities such as neutropenia and mucositis should be managed aggressively. Growth factors reduce the incidence and severity of neutropenia and its complications in older patients, particularly when they are administered in the early cycles of chemotherapy. The development of effective strategies for the management of toxicity caused by anticancer drugs may help the elderly, as much as younger patients, expect and look forward to a positive outcome with their treatment.
The journal of supportive oncology 11/2003; 1(4 Suppl 2):30-7.
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