Dose response evaluation of adriamycin in human neoplasia

O'Bryan, Robert M.; Baker, Laurence H.; Gottlieb, Josh; Rivkin, Saul E.; Balcerzak, Stanley P.; Grumet, G. N.; Salmon, Sydney E.; Moon, Thomas E.; Hoogstraten, Barth

doi:10.1002/1097-0142(197705)39:5<1940::aid-cncr2820390505>3.0.co;2-0

Cited by 353 publications

(83 citation statements)

References 11 publications

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“…Comparison between mdrl and gst-7 mRNA levels in all the breast samples assayed shows a low level of correlation which is only slightly significant (r = 0.48, P <0.1). Thus for some of these tumours coexpression of Discussion Doxorubicin is widely used in the treatment of advanced breast cancer, with an overall response rate among breat cancer patients of about 55% (Blum & Carter, 1974;O'Bryan et al, 1977). This means that almost half the patients are resistant to doxorubicin from the outset of treatment.…”

Section: Methodsmentioning

confidence: 94%

“…However, both inherent and acquired resistance are in many cases major obstacles in successful treatment (O'Bryan et al, 1977). Increased levels of expression of the mdrl gene, which codes for a 175 kDa plasma membrane associated glycoprotein, and the gst-rc gene, encoding the anionic isozyme of glutathione Stransferase (GSTh) have previously been shown in doxorubicin (adriamycin) resistant cell lines, derived by drug selection in culture Riordan et al, 1985;Scotto et al, 1986;Cowan et al, 1986;Deffie et al, 1988;Van der Bliek et al, 1988).…”

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confidence: 99%

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Expression of mdr1 and gst-π in human breast tumours: comparison to in vitro chemosensitivity

Keith¹,

Stallard²,

Brown³

1990

Br J Cancer

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Section: Methodsmentioning

confidence: 94%

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confidence: 99%

Expression of mdr1 and gst-π in human breast tumours: comparison to in vitro chemosensitivity

Keith¹,

Stallard²,

Brown³

1990

Br J Cancer

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“…Doxorubicin and ifosfamide are considered the cornerstones of treatment for advanced STS, consistently producing responses as monotherapy in more than 20% of previously untreated patients (Pinedo and Kenis, 1977). Most studies have demonstrated a clear doseresponse relationship for both of these drugs (O'Bryan et al, 1977, Antman et al, 1990. Combinations of the active drugs have shown improved response rates, but are often limited by increased toxicity (Benjamin, 1987).…”

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confidence: 99%

Combination of pegylated liposomal doxorubicin (PLD) and paclitaxel in patients with advanced soft tissue sarcoma: a phase II study of the Hellenic Cooperative Oncology Group

et al. 2004

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Patients with soft tissue sarcoma (STS), even after complete local disease control, often relapse locally or with distant metastases. This multicenter phase II study was conducted to evaluate the safety and efficacy of the combination of pegylated liposomal doxorubicin (PLD) and paclitaxel, as first-line treatment in patients with advanced STS. In all, 42 patients with locally advanced or metastatic STS, median age 54 years and median Eastern Cooperative Oncology Group performance status (PS) 1 were treated with PLD 45 mg m À2 and paclitaxel 150 mg m À2 , every 28 days for a total of six cycles. Histological types included mainly leiomyosarcomas (43%), malignant fibrous histiocytomas (14%) and liposarcomas (12%). At study entry, 69% of patients had distant metastases. Overall response rate was 16%, including one complete (CR 2%) and six partial responses (PRs 14%), while an additional 14 patients had disease stabilization (SD 33%). At median follow-up 41.5 months, median time to progression (TTP) was 5.7 months with median overall survival (OS) 13.2 months. Grade 3 -4 toxicities included neutropenia (17%), anaemia (15%), neurotoxicity (5%) and palmarplantar erythrodysesthesia (9%). There were no treatment-related deaths. The combination of PLD and paclitaxel is a safe and welltolerated regimen demonstrating modest efficacy as first-line treatment in patients with advanced STS.

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“…6,7 There is strong evidence for a dose-response relationship for doxorubicin and ifosfamide. 8,9 For optimal response rates it seems essential to achieve a dose intensity of greater than 65 mg/m 2 for doxorubicin and greater than 5 g/m 2 for ifosfamide. 10,11 In the last decade, hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have entered clinical trials in an attempt to administer escalated-dose chemotherapy regimens without inducing fatal neutropenia.…”

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confidence: 99%

Mobilization of peripheral blood progenitor cells by disease-specific chemotherapy in patients with soft tissue sarcoma

Schwella

Rick

Meyer

et al. 1998

Bone Marrow Transplant

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Summary:We investigated peripheral blood progenitor cell (PBPC) mobilization by disease-specific chemotherapy in patients with metastatic soft tissue sarcoma (STS). Nine patients, five females and four males, aged 12-51 years, pretreated by one to nine courses of cytotoxic chemotherapy, underwent STS-specific mobilization followed by G-CSF at 5 g/kg/day. PBPC were collected by 19 conventional-volume aphereses (8-12 l) with one to four procedures in individual patients. Leukaphereses started on median day 15 (range 13-18) from the first day of mobilization chemotherapy at medians of 25.8 ؋ 10 3 WBC/ l (6.8-46.9), 3.5 ؋ 10 3 MNC/ l (1.1-8.8), 122 ؋ 10 3 platelets/ l (72-293) and 30.7 CD34 ؉ cells/ l (6.7-207.8). Cumulative harvests resulted in medians of 4.6 ؋ 10 8 MNC/kg (3.0-6.4), 2.9 ؋ 10 6 CD34 ؉ cells/kg (1.1-11.1) and 12.0 ؋ 10 4 CFU-GM/kg (2.0-37.8). Eight patients underwent high-dose chemotherapy (HDCT) followed by PBPC rescue. Seven patients recovered hematopoiesis at medians of 12 days (8-15) for ANC Ͼ0.5 ؋ 10 3 / l and 14 days (8-27) for platelets Ͼ20 ؋ 10 3 / l. One patient, who received 1.6 ؋ 10 6 CD34 ؉ cells/kg, exhibited delayed ANC recovery on day ؉37 and failed to recover platelets until hospital discharge on day +55. We conclude that in patients with metastatic STS, who are pretreated by standard chemotherapy, PBPC can be mobilized by a further course of STS-specific chemotherapy plus G-CSF. One to four conventional-volume aphereses result in PBPC autografts that can serve as hematopoietic rescue for patients scheduled for HDCT. Keywords: soft tissue sarcoma; blood progenitor cells; disease-specific mobilization Soft tissue sarcomas (STS), arising from the extraskeletal connective tissue of the body, occur at a rate of 0.7% of all adult cancers. 1 Radical surgery, often combined with radiotherapy, can be curative in up to 60% of patients. However, prognosis of patients with metastatic or recurrent STS is poor, and most of them will die from progressive Treatment of patients who do not respond to these drugs is very difficult because only few salvage regimens exist. 6,7 There is strong evidence for a dose-response relationship for doxorubicin and ifosfamide. 8,9 For optimal response rates it seems essential to achieve a dose intensity of greater than 65 mg/m 2 for doxorubicin and greater than 5 g/m 2 for ifosfamide. 10,11 In the last decade, hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have entered clinical trials in an attempt to administer escalated-dose chemotherapy regimens without inducing fatal neutropenia. 12,13 More recently, the use of hematopoietic stem/progenitor cells has circumvented myelotoxicity as the dose-limiting toxicity in clinical trials. 14,15 The aim of this study was to demonstrate peripheral blood progenitor cell (PBPC) mobilization by diseasespecific chemotherapy in pretreated patients with metastatic STS scheduled for high-dose chemotherapy (HDCT). Patients and methods Pa...

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Dose response evaluation of adriamycin in human neoplasia

Cited by 353 publications

References 11 publications

Expression of mdr1 and gst-π in human breast tumours: comparison to in vitro chemosensitivity

Expression of mdr1 and gst-π in human breast tumours: comparison to in vitro chemosensitivity

Combination of pegylated liposomal doxorubicin (PLD) and paclitaxel in patients with advanced soft tissue sarcoma: a phase II study of the Hellenic Cooperative Oncology Group

Mobilization of peripheral blood progenitor cells by disease-specific chemotherapy in patients with soft tissue sarcoma

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