Activity of 2, 2 -difluorodeoxycytidine (Gemcitabine) against human tumor colony forming units

Ar, Hanauske; Degen, D; Mh, Marshall; Sg, Hilsenbeck; Gb, Grindey; Hoff, Von

doi:10.1097/00001813-199204000-00012

Cited by 23 publications

(8 citation statements)

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“…[12] Preclinical experiments indicate that the antitumor effect of gemcitabine is highly dependent on both its dose and duration of exposure. [14–16] Gemcitabine causes limited extramedullary toxicity at standard doses and shows clinical antitumor activity against HL [17,18] and NHL. [19,20] Therefore, it presents a promising profile for combination with alkylators in HDC studies for lymphomas.…”

Section: Introductionmentioning

confidence: 99%

High-Dose Infusional Gemcitabine Combined with Busulfan and Melphalan with Autologous Stem-Cell Transplantation in Patients with Refractory Lymphoid Malignancies

Nieto

Thall

Valdez

et al. 2012

Biology of Blood and Marrow Transplantation

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We developed a new high-dose combination of infusional gemcitabine with busulfan/melphalan for lymphoid tumors. Gemcitabine dose was escalated by extending infusions at a fixed rate of 10 mg/m2/min in sequential cohorts, in daily, 3-dose or 2-dose schedules. Each dose immediately preceded busulfan (adjusted targeting AUC 4,000 μM.min−1/day × 4 days) or melphalan (60 mg/m2/day × 2 days). We enrolled 133 patients (80 Hodgkin’s lymphoma (HL), 46 non-Hodgkin’s lymphoma (NHL), 7 myeloma), median 3 prior regimens; primary refractory disease in 63% HL/45% NHL and PET-positive tumors at transplant in 50% patients. Two patients died from early posttransplant infections. The major toxicity was mucositis. The daily and 3-dose schedules caused substantial cutaneous toxicity. In contrast, the 2-dose schedule was better tolerated, which allowed us to extend the infusions from 15 to 270 minutes. Pretransplant values of C-reactive protein, b-type natriuretic peptide, ferritin or haptoglobin did not correlate with toxicity. Overall response and complete response rates were 87%/62% (HL), 100%/69% (B-LCL), 66%/66% (T-NHL), and 71%/57% (myeloma). At median follow-up of 24 months (3–63), the event-free/overall survival rates are 54%/72% (HL), 60%/89% (B-LCL), 70%/70% (T-NHL) and 43%/43% (myeloma). In conclusion, gemcitabine/busulfan/melphalan is a feasible regimen with substantial activity against a range of lymphoid malignancies. This regimen merits further evaluation in phase II and III trials.

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Section: Introductionmentioning

confidence: 99%

High-Dose Infusional Gemcitabine Combined with Busulfan and Melphalan with Autologous Stem-Cell Transplantation in Patients with Refractory Lymphoid Malignancies

Nieto

Thall

Valdez

et al. 2012

Biology of Blood and Marrow Transplantation

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“…With the discovery of gemcitabine and its entry into phase I clinical trials, the San Antonio team began studying the activity of gemcitabine in a human tumour cloning assay (Hanauske et al, 1992;Von Hoff, 1996). This was carried out to help select the most appropriate schedule for phase I trials, to predict target plasma concentrations that must be achieved to have anti-tumour activity and to select the tumour types against which the new agent should be targeted in future phase II studies.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…This was carried out to help select the most appropriate schedule for phase I trials, to predict target plasma concentrations that must be achieved to have anti-tumour activity and to select the tumour types against which the new agent should be targeted in future phase II studies. Using both growth of human tumour colony-forming units in capillary tubes (Hanauske et al, 1992) and in Petri dishes (Von Hoff, 1996), gemcitabine demonstrated a very broad spectrum of anti-tumour activity with a concentration-response effect against non-small-cell lung, breast, ovarian and pancreatic cancer colony-forming units. Based on these results, gemcitabine was predicted to have a broad spectrum of anti-tumour activity; a prediction subsequently borne out in follow-up clinical trials.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Advances in the treatment of patients with pancreatic cancer: improvement in symptoms and survival time

Hoff

Goodwin²,

Garcia³

1998

Br J Cancer

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Summary Pancreatic cancer is a major cause of death from cancer in both men and women in the USA and Europe. The disease causes pain and has a significant impact on the performance status of the patient. In a randomized trial vs 5-fluorouracil, the novel nucleoside analogue gemcitabine (GEMZAR®) has been shown to provide clinical benefit for patients (decreased pain and improved performance status) as well as to improve the time to tumour progression and survival for patients with the disease. There are also other new agents that are presented in this discussion, such as the multi-targeted antifolate MTA, capecitabine and the ONYX-015 adenovirus, which replicates in, and kills, only p53-abnormal cells, which have the potential to have an impact on this terrible disease.

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“…Gemcitabine was found to be 100-times more active than cytarabine after incubation periods of 2 and 24 hours in cell lines of human myeloid HL-60, T-lymphoid Molt-3, and B-lymphoid RPMI-8392. [3] Pharmacokinetics were linear with plasma peak level and the area-under-the-concentration-time curve was proportional to the administered dose. Gemcitabine is deaminated by the liver and kidney with rapid elimination and a median half-life of 8.0 minutes.…”

Section: Introductionmentioning

confidence: 98%

A Phase I Study of Gemcitabine and Docetaxel for Advanced Stage Solid Tumors

Poole

Bernard

Churchel³

et al. 2003

Cancer Investigation

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Activity of 2, 2 -difluorodeoxycytidine (Gemcitabine) against human tumor colony forming units

Cited by 23 publications

References 0 publications

High-Dose Infusional Gemcitabine Combined with Busulfan and Melphalan with Autologous Stem-Cell Transplantation in Patients with Refractory Lymphoid Malignancies

High-Dose Infusional Gemcitabine Combined with Busulfan and Melphalan with Autologous Stem-Cell Transplantation in Patients with Refractory Lymphoid Malignancies

Advances in the treatment of patients with pancreatic cancer: improvement in symptoms and survival time

A Phase I Study of Gemcitabine and Docetaxel for Advanced Stage Solid Tumors

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