Factors Determining the Actual Received Dose Intensity in a Program of Multicyclic Dose-Intensive Alternating Chemotherapy with Sequential Stem Cell Support

Pérez‐Calvo, Javier; Martínez-Aguillo, Maite; García-Rayo, S; Cajal, Teresa Ramón y; Santisteban, Marta; Ordóñez, José Manuel; Inogés, Susana; Subirá, María L.; Martín‐Algarra, Salvador; Brugarolas, Antonio

doi:10.1159/000046555

Cited by 1 publication

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“…In a multivariate analysis, we found the CD34 + cell dose to be a significant predictor of the actual administered dose intensity. 22 Nevertheless, above certain threshold values of cells, further increases in the CD34 dose may not lead to further significant decreases in the interval. 14,22 A similar effect has been described in single autografts with stem cell support, where recoveries are never reached before certain points (8 to 9 days post infusion), regardless of the CD34 + cell dose administered.…”

Section: Discussionmentioning

confidence: 99%

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Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study

García-Rayo

Pérez‐Calvo

Martín‐Algarra

et al. 2001

Bone Marrow Transplant

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Summary:The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. ades. Extensive literature reviews by Hryniuk et al 1,2 have found dose intensity to be correlated with response rate and survival. This effect has been considered in the rationale of many clinical trials that attempted to improve long-term survival in metastatic BC by delivering single courses of high-dose chemotherapy (HDC). Despite some promising data derived from phase II trials, results of the randomized studies published thus far have failed to show a sound clinical benefit for single autografts. [3][4][5] There might be other ways to take advantage of the doseintensity principle. In vitro, repeated doses of chemotherapy cause more cell kill than single doses, even though the total amount of drug administered is the same. 6 The classical model of Gompertzian kinetics provides a possible explanation for this fact through rapid compensatory re-growth of the resistant clones not eradicated by HDC. 7 The spread of the cytotoxic effect over a longer period of time might increase cell kill and reduce the probability of drug resistance. 8 Multicyclic treatment schemes appear to take advantage of the inherent time-dependant responsiveness of most cancer tissues.Autologous peripheral blood stem cell infusions have been extensively used to support single courses of HDC. Nonetheless, their possible use in programs of multicyclic non-myeloablative dose-intense chemotherapy has been little explored. [9][10][11][12] In November 1995, the Department of Oncology of University of Navarra, Spain, initiated a feasibility study that included a biweekly, alternating, doseintensive chemotherapy regimen. The results observed in the first 43 patients with metastatic BC are presented in this report. Materials and methodsWomen with histologically proven metastatic BC were evaluated for study entry. An ECOG performance status of 0-1, age less than 65 years, and no evidence of cardiac, pulmonary, liver or renal impairment were required. All patients gave written informed consent according to institutional policy before entering the study. Patients presenting with brain metastases, leptomeningeal disease, or bone marrow involvement, as well as patients previously

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Section: Discussionmentioning

confidence: 99%

“…Median duration of response was 12 months (95% CI, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Recurrences have been observed predominantly in areas with previous bulky disease (75% of cases).…”

Section: Sites Of Relapse After Sictmentioning

confidence: 99%