Conventional-Dose Chemotherapy Compared with High-Dose Chemotherapy plus Autologous Hematopoietic Stem-Cell Transplantation for Metastatic Breast Cancer

Stadtmauer, Edward A.; O’Neill, Anne; Goldstein, Lori J.; Crilley, Pamela; Mangan, Kenneth F.; Ingle, James N.; Brodsky, Isadore; Martino, Silvana; Lazarus, Hillard M.; Erban, John K.; Sickles, Cheryl; Glick, John H.

doi:10.1056/nejm200004133421501

Cited by 390 publications

(209 citation statements)

References 15 publications

(13 reference statements)

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“…The widely employed STAMP-V regimen, a combination of cyclophosphamide, thiotepa and carboplatin (CTC), has been reported to be well tolerated (Antman et al, 1992). STAMP-V has been employed in several large randomised studies in breast cancer (Bergh et al, 2000;Stadtmauer et al, 2000), none of which showed a (progression-free) survival advantage for the patients receiving this treatment.…”

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confidence: 99%

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

et al. 2003

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High-dose chemotherapy (HD-CT) has a role in the potentially curative treatment of several tumours. The relative efficacies of the different regimens have not been studied in comparative trials, but it is clear that toxicities differ significantly between them. We analysed the immediate and long-term toxicity in the first 100 consecutive patients treated with the CTC regimen (cyclophosphamide 6000 mg m À2 , carboplatin 1600 mg m À2 (or 20 mg ml À1 min under the curve (AUC)) both as daily 1 h infusion, thiotepa 480 mg m À2 as twice daily 30 min infusion, all divided over 4 consecutive days) followed by peripheral blood progenitor cell reinfusion (PBPC-Tx). Most patients had high-risk (n ¼ 86) or metastatic (n ¼ 4) breast cancer, or a germ cell tumour (n ¼ 8). Two patients (with a medulloblastoma and an aesthesioneuroblastoma, respectively) received CTC as off-protocol salvage regimen. The main toxicity was bone marrow suppression. Most patients had PBPC-Tx with granulocyte colony-stimulating factor (G-CSF), and the median time to neutrophil count 500 Â 10 6 l À1 and platelet count 420 Â 10 9 l À1 without transfusion independence was 10 (range 8 -25) and 13 (8 -60) days, respectively. The toxic death rate was 1%. Other frequent toxicities were neutropenic fever requiring antibiotics (n ¼ 65), central catheter-related infection (n ¼ 12) or a bleeding episode (n ¼ 48), mostly epistaxis (n ¼ 26). Reversible cardiac toxicity was seen in six patients and pulmonary events occurred in seven patients (infection (n ¼ 6), embolism (n ¼ 1)). Grade 3 -4 gastrointestinal toxicity was frequent: nausea and vomiting 55%, diarrhoea 28% and mild liver toxicity (transaminase elevations) 9%. One patient pretreated with cisplatin had a kidney transplantation 8 years after HD-CT. Late complications included reversible radiation pneumonitis (n ¼ 12) and chronic heart failure (n ¼ 2). We found five second solid malignancies and two myelodysplasias. In conclusion, the CTC regimen is associated with a moderate, mainly reversible, toxicity. Future studies need to compare the efficacy and toxicity of the different HD-CT regimens.

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Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

et al. 2003

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“…On the basis of so far 3 reported randomized studies (Peters et al, 1996;Lotz et al, 1999;Stadtmauer et al, 2000), the value and feasibility of HDC in metastatic breast cancer has been extensively and critically reviewed (Antman, 1999;Crown et al, 1999;Gradishar, 1999;Hortobagyi, 1999;Livingston and Crowley, 1999;MacNeil and Eisenhauer, 1999). The negative PBT-1 trial (Stadtmauer et al, 2000), which included the largest number of patients, has been widely commented: from 553 patients initially included in the study, only 199 (of whom only 45 CR patients) were amenable to randomization.…”

Section: Discussionmentioning

confidence: 99%

“…The negative PBT-1 trial (Stadtmauer et al, 2000), which included the largest number of patients, has been widely commented: from 553 patients initially included in the study, only 199 (of whom only 45 CR patients) were amenable to randomization. The imbalance between the prognostic factors of the 2 arms, favouring the control arm, has also been questioned (Antman, 1999), as well as the concern about the standard arm of continuous CMF (MacNeil and Eisenhauer, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…After 1990, haematologic support with haematopoietic growth factors (G-CSF and GM-CSF) and blood cells progenitors derived from the bone marrow (ABMT) or from peripheral blood (PBSC) became widely available to circumvent the dose-limiting haematological toxicity and infectious complications. Many studies of high-dose chemotherapy (HDC) with G-CSF and ABMT/PBSC have been published, including studies dealing with HDC multicycle regimens (Rodenhuis et al, 1996;Vahdat and Antman, 1997), and 3 randomized studies (Peters et al, 1996;Lotz et al, 1999;Stadtmauer et al, 2000). Most of these regimens included only alkylating agents (Peters et al, 1996;Rodenhuis et al, 1996;Antman et al, 1997;Vahdat and Antman, 1997;Stadtmauer et al, 2000), only 3% of them including mitoxantrone in the conditioning combination Vahdat and Antman, 1997;Lotz et al, 1999).…”

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confidence: 99%

“…Many studies of high-dose chemotherapy (HDC) with G-CSF and ABMT/PBSC have been published, including studies dealing with HDC multicycle regimens (Rodenhuis et al, 1996;Vahdat and Antman, 1997), and 3 randomized studies (Peters et al, 1996;Lotz et al, 1999;Stadtmauer et al, 2000). Most of these regimens included only alkylating agents (Peters et al, 1996;Rodenhuis et al, 1996;Antman et al, 1997;Vahdat and Antman, 1997;Stadtmauer et al, 2000), only 3% of them including mitoxantrone in the conditioning combination Vahdat and Antman, 1997;Lotz et al, 1999). A fourth randomized study had been published earlier (Bezwoda et al, 1995), but an international audit has demonstrated that 'the multiple publications of this study (...) do not report verifiable data' (Weiss et al, 2001).…”

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High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study

Cottu

Espié

et al. 2001

Br J Cancer

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SummaryThe aim of this study was to evaluate the feasibility of a high-dose intensity and high-dose density multicycle epirubicin and cyclophosphamide regimen with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to September 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) received 205 courses of cyclophosphamide 3 g m -2 and epirubicin 100 mg m -2 every 14 days. G-CSF 5 µg kg -1 day -1 was administered from day 3 to neutrophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, with ≥ 2 × 10 6 CD34+ PBSC kg -1 required for each reinfusion. 48 patients (86%) received all 4 planned courses. Early withdrawal was consecutive to infectious complications (n = 4), severe asthenia (n = 3), haemorrhagic cystitis (n = 1). A median number of 10.8 × 10 6 CD34+ PBSC kg -1 (range, 3-80) was harvested with 1 or 2 apheresis in 48 patients (94%). Median relative dose intensity was 91.3% (range, 72-102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (median duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Objective response rate was 69% in stage IV patients (31/45 evaluable pts), with a 16% complete response rate. Their median progression-free and overall survivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-related progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate its real benefit.

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The Promise of Comparative Effectiveness Research

Sullivan¹

2011

JAMA

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Medicare must find new ways to achieve cost control without limiting access to beneficial services. We propose a payment model incorporating comparative effectiveness research to encourage Medicare to pay equally for services that provide comparable patient outcomes. The model would include higher payments for services demonstrated by adequate evidence to provide superior health benefits compared to alternative options. New services without such evidence would receive usual reimbursement rates for a limited time but then be reevaluated as evidence emerged. In spite of the substantial political hurdles to changing Medicare reimbursement, efforts should be made to use comparative effectiveness research to reward superior services, improve incentives for cost-effective innovation, and place Medicare on a more sustainable financial footing.

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Conventional-Dose Chemotherapy Compared with High-Dose Chemotherapy plus Autologous Hematopoietic Stem-Cell Transplantation for Metastatic Breast Cancer

Cited by 390 publications

References 15 publications

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study

The Promise of Comparative Effectiveness Research

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