Intensified CHOP regimen in aggressive lymphomas:maximal dose intensity and dose density of doxorubicin and cyclophosphamide

Balzarotti, Monica; Spina, Michele; Sarina, Barbara; Magagnoli, Massimo; Castagna, Luca; Milan, Isabella; Ripa, C.; Latteri, Federica; Bernardi, Daniele; Bertuzzi, Alexia; Nozza, Andrea; Roncalli, Massimo; Morenghi, Emanuela; Tirelli, Umberto; Santoro, Armando

doi:10.1093/annonc/mdf242

Cited by 25 publications

(10 citation statements)

References 18 publications

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“…In our study, RDI had a statistically significant effect on response rate but apparently not on overall survival; the latter finding might be jeopardized by the relatively short median follow-up duration (14.4 months) as 46% of the patients were still alive at the time of analysis. Several studies in specific tumor settings have tested the role of DI on different outcomes such as response rate, progression-free survival and overall survival [6, 7, 9,21,22,23,24,25,26], and some tumors as melanomas, small-cell lung cancers, breast cancers and non-Hodgkin lymphomas are reported to be sensitive to increased DI [5, 7, 21,26,27,28,29,30,31,32,33]. While highly selected elderly patients enrolled in clinical trials can achieve a DI comparable to the younger ones [34], in common clinical practice, when using conventional chemotherapy regimens, elderly patients rarely achieve an adequate DI [35, 36].…”

Section: Discussionmentioning

confidence: 99%

Do Elderly Cancer Patients Achieve an Adequate Dose Intensity in Common Clinical Practice?

Luciani¹,

Marussi²,

Ascione³

et al. 2006

Oncology

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Background: Elderly patients rarely receive adequate dose intensity (DI) using conventional regimens. Possible causes are improper patient assessment, the chemotherapy (CT) regimen chosen, the number and severity of comorbidities, patient compliance and physician experience. To explore this issue, DI was retrospectively analyzed in elderly patients treated with conventional CT regimens for advanced solid cancer. Patients and Methods: Patients ≧69 years were evaluated. All patients had metastatic solid tumors. Comorbidities, performance status (PS), toxicities, number of CT cycles, dose reduction and discontinuation of treatment were recorded. Relative DI (RDI) was calculated and regressed against these parameters. Results: 108 patients were eligible. The most frequent diagnoses were: lung, head-and-neck and colorectal cancer. In 48 patients (44%), their initially scheduled treatment was modified. Mean RDI was 79% (range 19–100%, SD 20.6). Grade 3/4 non-hematological and hematological toxicity occurred in 27 (35/130) and 8% of patients (11/130), respectively. In regression analysis, RDI was significantly associated with hematological toxicity. RDI affected response rate but not overall survival. Conclusions: RDI is significantly affected by toxicity. These data suggest the importance of the treatment schedule and patient selection as predictorsof adequate treatment. Some non-ratable variables, however, might also play a role regarding the dose intensity delivered.

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Section: Discussionmentioning

confidence: 99%

Do Elderly Cancer Patients Achieve an Adequate Dose Intensity in Common Clinical Practice?

Luciani¹,

Marussi²,

Ascione³

et al. 2006

Oncology

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“…In recent years, two strategies have improved the outcome of patients with aggressive lymphoma. The first was the use of rituximab, a monoclonal anti-CD20 antibody, in addition to the CHOP scheme [8]; the second was the increase of the dose density of CHOP by shortening the interval between cycles from 3 to 2 weeks [9, 10]. These two strategies provided better disease-free survival, overall survival and response.…”

Section: Introductionmentioning

confidence: 99%

Dose-Dense CHOP plus Rituximab (R-CHOP14) for the Treatment of Elderly Patients with High-Risk Diffuse Large B Cell Lymphoma: A Pilot Study

Rigacci

Nassi²,

Alterini³

et al. 2006

Acta Haematol

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Background: Aggressive non-Hodgkin’s lymphomas (NHL) require intensive therapies which seemed impracticable in elderly patients. Dose reduction and therapy attenuation reduced treatment-related toxicity, but also decreased therapeutic efficacy. In elderly patients too, the achievement of complete remission is the most important prognostic factor affecting outcome. Therefore, we have treated elderly patients with a dose-intensified protocol. Aim of the study was to verify the feasibility of this scheme in a subset of patients with high-risk aggressive lymphomas. Methods: Between June 2002 and June 2004, 26 patients over the age of 60 years with a diagnosis of aggressive NHL and an intermediate-high or high International Prognostic Index were treated with biweekly CHOP plus rituximab with the support of granulocyte colony-stimulating factors (G-CSF). Results: Seventeen patients (65%) regularly kept the interval between cycles. Haematological and extrahaematological toxicities were moderate in all the patients. Twenty (77%) patients achieved complete remissions, 6 (23%) partial remissions with an overall response rate of 100%. After a median follow-up of 23 months, the overall survival was 79%; after a median follow-up of 17 months, the disease-free survival was 70%. Conclusion: These results confirm that a dose-dense CHOP programme can be administered safely and effectively in a subset of elderly patients with high-risk aggressive NHL. The addition of rituximab could increase the response rate without adding toxicity.

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“…This result could be clearly observed in all simulated cases. The existence of CI, and the inability to maintain the regimen intensity above it, may account for the disappointing results of regimen intensification in some clinical trials [8], as opposed to its success in others [12]. These results further elaborate on the dose intensity paradigm, which has been put forward by Norton [37]: It does not suffice to simply increase the regimen intensity; it must be kept above a certain critical value.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of patients are treated with the CHOP [12] chemotherapy regimen, consisting of 4-8 treatment cycles administered at 21-day intervals. Despite several decades of clinical investigation, CHOP remains the first line treatment in NHL [8]. Several questions concerning NHL chemotherapy remain as yet unresolved.…”

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confidence: 99%

Intensified Doxorubicin-Based Regimen Efficacy in Residual Non-Hodgkin's Lymphoma Disease: Towards a Computationally Supported Treatment Improvement

Kogan

Ribba

Marron

et al. 2007

Math. Model. Nat. Phenom.

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Abstract. Despite recent advances, treatment of patients with aggressive Non-Hodgkin's lymphoma (NHL 2 ) has yet to be optimally designed. Notwithstanding the contribution of molecular treatments, intensification of chemotherapeutic regimens may still be beneficial. Hoping to aid in the design of intensified chemotherapy, we put forward a mathematical and computational model that analyses the effect of Doxorubicin on NHL over a wide range of patho-physiological conditions. The model represents tumour growth both in diffusion-limited settings, that is, in small avascular tumours and tumour cords, and in perfusion-limited settings, e.g. in well-vascularized tumours. Model simulations indicated the presence of a critical regimen intensity below which treatment will fall short of tumour elimination. Taking this critical intensity into account, we compared two regimen intensification strategies: Dose escalation and regimen densification, i.e. reducing the inter-dosing interval. In the diffusion-limited setting, dose escalation was somewhat more efficient than regimen densification. In the perfusion-limited setting, both intensification strategies yielded similar results. The present study coupled with a realistic myelotoxicity model may add insight on the optimisation of NHL intensified chemotherapy design.

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Intensified CHOP regimen in aggressive lymphomas:maximal dose intensity and dose density of doxorubicin and cyclophosphamide

Abstract: This intensified CHOP regimen is feasible on an outpatient basis. It can be safely considered a definitive treatment in patients at low and intermediate risk, and as induction before high-dose consolidation in high-risk cases.

Cited by 25 publications

References 18 publications

Do Elderly Cancer Patients Achieve an Adequate Dose Intensity in Common Clinical Practice?

Do Elderly Cancer Patients Achieve an Adequate Dose Intensity in Common Clinical Practice?

Dose-Dense CHOP plus Rituximab (R-CHOP14) for the Treatment of Elderly Patients with High-Risk Diffuse Large B Cell Lymphoma: A Pilot Study

Intensified Doxorubicin-Based Regimen Efficacy in Residual Non-Hodgkin's Lymphoma Disease: Towards a Computationally Supported Treatment Improvement

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