8 research outputs found
Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study
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. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m2 plus doxorubicin 80 mg/m2 alternating every 14 days with paclitaxel 200-350 mg/m2 plus cisplatin 120 mg/m2. Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m2 plus etoposide 600 mg/m2 alternating with paclitaxel 200-350 mg/m2 plus ifosfamide 8 g/m2. Peripheral blood stem cells were infused after every course except the first, with a median CD34+ dose of 2.1 ´ 106/kg per cycle. Positive selection of CD34+ cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support
Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study
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. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m2 plus doxorubicin 80 mg/m2 alternating every 14 days with paclitaxel 200-350 mg/m2 plus cisplatin 120 mg/m2. Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m2 plus etoposide 600 mg/m2 alternating with paclitaxel 200-350 mg/m2 plus ifosfamide 8 g/m2. Peripheral blood stem cells were infused after every course except the first, with a median CD34+ dose of 2.1 ´ 106/kg per cycle. Positive selection of CD34+ cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics
Hyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting of an
acceleration of tumor growth associated with prompt clinical deterioration. The definitions based on
radiological evaluation present important technical limitations. No biomarkers have been identified
yet. In this study, 70 metastatic NSCLC patients treated with anti-PD-1/PD-L1 immunotherapy
after progression to platinum-based therapy were prospectively studied. Samples from peripheral
blood were obtained before the first (baseline) and second cycles of treatment. Peripheral blood
mononuclear cells (PBMCs) were isolated and differentiation stages of CD4 lymphocytes quantified
by flow cytometry and correlated with HPD as identified with radiological criteria. A strong
expansion of highly differentiated CD28− CD4 T lymphocytes (CD4 THD) between the first and
second cycle of therapy was observed in HPD patients. After normalizing, the proportion of
posttreatment/pretreatment CD4 THD was significantly higher in HPD when compared with the
rest of patients (median 1.525 vs. 0.990; p = 0.0007), and also when stratifying by HPD, non-HPD
progressors, and responders (1.525, 1.000 and 0.9700 respectively; p = 0.0025). A cut-off value of 1.3
identified HPD with 82% specificity and 70% sensitivity. An increase of CD28− CD4 T lymphocytes ≥
1.3 (CD4 THD burst) was significantly associated with HPD (p = 0.008). The tumor growth ratio (TGR)
was significantly higher in patients with expansion of CD4 THD burst compared to the rest of patients
(median 2.67 vs. 0.86, p = 0.0049), and also when considering only progressors (median 2.67 vs. 1.03,
p = 0.0126). A strong expansion of CD28− CD4 lymphocytes in peripheral blood within the first
cycle of therapy is an early differential feature of HPD in NSCLC treated with immune-checkpoint inhibitors. The monitoring of T cell dynamics allows the early detection of this adverse outcome in
clinical practice and complements radiological evaluation
Early Detection of Hyperprogressive Disease in Non-Small Cell Lung Cancer by Monitoring of Systemic T Cell Dynamics
Hyperprogressive disease (HPD) is an adverse outcome of immunotherapy consisting of an
acceleration of tumor growth associated with prompt clinical deterioration. The definitions based on
radiological evaluation present important technical limitations. No biomarkers have been identified
yet. In this study, 70 metastatic NSCLC patients treated with anti-PD-1/PD-L1 immunotherapy
after progression to platinum-based therapy were prospectively studied. Samples from peripheral
blood were obtained before the first (baseline) and second cycles of treatment. Peripheral blood
mononuclear cells (PBMCs) were isolated and differentiation stages of CD4 lymphocytes quantified
by flow cytometry and correlated with HPD as identified with radiological criteria. A strong
expansion of highly differentiated CD28− CD4 T lymphocytes (CD4 THD) between the first and
second cycle of therapy was observed in HPD patients. After normalizing, the proportion of
posttreatment/pretreatment CD4 THD was significantly higher in HPD when compared with the
rest of patients (median 1.525 vs. 0.990; p = 0.0007), and also when stratifying by HPD, non-HPD
progressors, and responders (1.525, 1.000 and 0.9700 respectively; p = 0.0025). A cut-off value of 1.3
identified HPD with 82% specificity and 70% sensitivity. An increase of CD28− CD4 T lymphocytes ≥
1.3 (CD4 THD burst) was significantly associated with HPD (p = 0.008). The tumor growth ratio (TGR)
was significantly higher in patients with expansion of CD4 THD burst compared to the rest of patients
(median 2.67 vs. 0.86, p = 0.0049), and also when considering only progressors (median 2.67 vs. 1.03,
p = 0.0126). A strong expansion of CD28− CD4 lymphocytes in peripheral blood within the first
cycle of therapy is an early differential feature of HPD in NSCLC treated with immune-checkpoint inhibitors. The monitoring of T cell dynamics allows the early detection of this adverse outcome in
clinical practice and complements radiological evaluation