A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy.

Antman, Karen H.; Ayash, Lois; Elias, Anthony; Wheeler, Catherine; Hunt, M; Eder, Joseph P.; Teicher, Beverly A.; Critchlow, J; Bibbo, J; Schnipper, Lowell E.

doi:10.1200/jco.1992.10.1.102

Cited by 359 publications

(137 citation statements)

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“…The objective of this analysis was to describe the early and late toxicities of this regimen, which is similar to but not identical with the CTCb (STAMP-V) regimen described by Antman et al (1992).…”

Section: Discussionmentioning

confidence: 99%

“…The two studies (Peters et al, 1993;Nikcevich et al, 2002) that employed this carmustine-based combination reported high toxic death rates due to organ toxicity, mainly interstitial pneumonitis. Even very experienced centres that optimally exploit corticosteroids at the earliest sign of pulmonary symptoms report a 5% toxic death rate (Antman et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…The STAMP-I regimen, for example, which incorporates cisplatin, cyclophosphamide and BCNU, is associated with a 12% mortality rate, mainly resulting from (BCNU-related) lung toxicity (Antman et al, 1997;Rosti and Ferrante, 2001). 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%

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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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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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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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“…The majority of patients (n = 9 in both arms) showed a TRF length decrease at t 1 , but also remarkable TRF length increases were observed; no significant decrease due to either treatment was found in paired samples. The high-dose treatment scheme used in this study is classically combined with stem cell support in view of its profound myolotoxicity, causing prolonged life threatening marrow aplasia (Ayash et al, 1993;Antman et al, 1994). It is possible that in individual patients the lack of TRF length decrease due to treatment may be interpreted as a sign of insufficient treatment toxicity, as stem cells remaining in the patient after high-dose treatment will have an impact on the requirements to divide for haematopoietic reconstitution.…”

Section: Discussionmentioning

confidence: 99%

Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

Schröder

Wisman²,

Jong³

et al. 2001

Br J Cancer

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High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) ( n = 17), or 4 × FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT ( n = 16). Haemoglobin, MCV, leukocyte-and platelet numbers were assessed prior to ( t 0 ), 5 months after ( t 1 ) and 9 months after chemotherapy ( t 2 ); these parameters were decreased at t 1 and t 2 compared to t 0 (high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t 1 . Paired individual leukocyte samples of t 0 and t 1 showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from +0.8 to –2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t 0 and t 1 . Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment. © 2001 Cancer Research Campaign www.bjcancer.com

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“…When given as adjuvant treatment for high-risk stage II -III breast cancer (six patients), HDCT consisted of cyclophosphamide, tiothepa, and carboplatin (CTCb) as previously described (Antman et al, 1992). An antracycline-containing regimen (fluorouracil, epirubicin and cyclophosphamide) (FEC-75) had been given as induction prior to HDCT.…”

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Responses to docetaxel plus vinorelbine in metastatic breast cancer patients failing high-dose chemotherapy

et al. 2002

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A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy.

Abstract: CTCb is an intensification regimen with a low mortality that delivers a significantly increased dose of agents with known activity at conventional doses in breast cancer. Although the duration of PR is short as expected, CRs appear to be durable.

Cited by 359 publications

References 29 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

Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

Responses to docetaxel plus vinorelbine in metastatic breast cancer patients failing high-dose chemotherapy

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