Studies With RP 56976 (Taxotere): A Semisynthetic Analogue of Taxol

Ringel, Israel; Horwitz, Susan Band

doi:10.1093/jnci/83.4.288

Cited by 609 publications

(279 citation statements)

References 0 publications

Supporting

Mentioning

268

Contrasting

Unclassified

Order By: Relevance

“…This induces a disruption of the equilibrium within the microtubule system and ultimately leads to cell death Ringel et al, 1991;. Docetaxel has been studied in many murine tumour models, showing activity against subcutaneous (s.c.) B16 melanoma, MX-l mammary cancer, C38 colon carcinoma, CX-1 colon carcinoma, LX-1 lung carcinoma, s.c. early stage pancreatic ductal adenocarcinoma (P03), S.C. colon adenocarcinoma 51 (C51), SK MEL-2 melanoma and OVCAR-3, HOC 8, HOC 10 and HOC 22 ovarian carcinomas (Denis et al, 1988;Bissery et al, 1991;Harrison et al, 1992, Nicoletti et al, 1992.…”

mentioning

confidence: 99%

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours

Pronk

Schrijvers²,

Schellens³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase 11 studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m-2 and ifosfamide doses from 2.5 to 5.0 g m-2. Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m-2 of docetaxel combined with 5.0 g m-2 ifosfamide appeared to be manageable. Schedule A was advocated for further treatment.

show abstract

mentioning

confidence: 99%

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours

Pronk

Schrijvers²,

Schellens³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…The anti-tumor mechanism of docetaxel is completely different from that of 5FU and CDDP (6). Docetaxel promotes the polymerization of tubulin and inhibits the disassembly of microtubules, thereby blocking cell division at the M phase during the cell cycle.…”

Section: Introductionmentioning

confidence: 98%

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

Tabuchi

Ozawa

Koyanagi

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Esophageal squamous cell carcinoma (ESCC)is more sensitive to radiation and chemotherapy than other cancers of the digestive system, and combined modality therapy may represent a promising treatment method. The radiation-sensitizing effect of docetaxel on ESCC cell lines was investigated. A colony formation assay was performed in which ESCC cell lines (TE2, TE3) and A431 were exposed to docetaxel (from 1.0x10 -11 to 10 -7 M) for 3 h to determine the concentration of docetaxel that was not able to kill individual cells (i.e., the non-cytocidal concentration). Individual cell lines were then exposed to the non-cytocidal concentration of docetaxel prior to, during, and after irradiation to determine whether the timing of docetaxel administration affected cell survival. In addition, flow-cytometry was performed, and the cell cycle was examined prior to and after docetaxel exposure to assess the mechanism of docetaxel as a radiation sensitizer. Docetaxel exhibited a concentration-dependent cytocidal effect, with a different IC 50 for each cell type. Almost no cytocidal effect was observed at the following docetaxel concentrations: A431, ≤1.0x10 -10 M; TE-2 and TE-3, ≤1.0x10 -9 M. Concurrent treatment with docetaxel and radiation tended to decrease cell survival in all the cell lines compared with docetaxel or radiation alone. Cell survival was lowest when the cells were treated using X-ray irradiation after docetaxel exposure (p<0.05). Flow cytometry revealed that in all three cell lines, docetaxel exposure increased the G2/M cell fraction with a higher increase in the cell line that exhibited the highest radiosensitivity. This study demonstrated that the administration of docetaxel at a non-cytocidal concentration prior to radiotherapy produced a synergistic cell-killing effect in SCC cell lines.

show abstract

“…This disruption of the normal equilibrium of tubulin function ultimately leads to cell death primarily during the G2/M-phase of the cell cycle [34]. As an inhibitor of microtubule depolymerization, docetaxel is approximately twice as potent as paclitaxel, prompting many investigators to study its cytotoxicity in a variety of cell lines [25]. Further clinical studies have shown docetaxel to have potent anti-tumor activity against several human tumors, including ovarian [20], anthracycline-resistant breast [4,30], non-small cell lung [6,10,12] and head and neck squamous cell cancer [7,31].…”

Section: Discussionmentioning

confidence: 99%

Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

et al. 2006

View full text Add to dashboard Cite

Docetaxel (Taxotere ® ) is a hemisynthetic, anti-cancer compound with good preclinical and clinical activity in a variety of systemic neoplasms. We tested its activity against malignant gliomas using local delivery methods. Antitumor activity was assessed in vitro against human and rat brain-tumor cell lines. For in vivo evaluation, we incorporated docetaxel into a biodegradable polymer matrix, determined associated toxicity in the rat brain, and measured efficacy at extending survival in a rat model of malignant glioma. Also, we examined the combined local delivery of docetaxel with carmustine (BCNU) against the experimental intracranial glioma. Rats bearing intracranial 9L gliosarcomas were treated 5 days after tumor implantation with various polymers (placebo, 5% docetaxel, 3.8% BCNU, or 5% docetaxel and 3.8% BCNU combination). Animals receiving docetaxel polymers (n = 15, median survival 39.1 days) had significantly improved survival over control animals (n = 12, median survival 22.5 days, P = 0.01). Similarly, animals receiving BCNU polymers (n = 15, median survival 39.3 days, 13.3% long-term survivors) demonstrated an increase in survival compared to the controls (P = 0.04). Animals receiving the combination polymers demonstrated a modest increase in survival compared to either chemotherapeutic agent alone (n = 14, median survival 54.9 days, 28.6% long-term survivors) with markedly improved survival over controls (P = 0.003). We conclude that locally delivered docetaxel shows promise as a novel antiglioma therapy and that the combination of drug regimens via biodegradable polymers may be a great therapeutic benefit to patients with malignant glioma.

show abstract

Studies With RP 56976 (Taxotere): A Semisynthetic Analogue of Taxol

Cited by 609 publications

References 0 publications

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

Interstitial Docetaxel (Taxotere), Carmustine and Combined Interstitial Therapy: a Novel Treatment for Experimental Malignant Glioma

Contact Info

Product

Resources

About