Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma.

Wiernik, Peter H.; Schwartz, Edward L.; Einzig, Avi I.; Strauman, Janice; Lipton, Richard B.; Dutcher, Janice P.

doi:10.1200/jco.1987.5.8.1232

Cited by 266 publications

(98 citation statements)

References 12 publications

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“…The paclitaxel levels reached a maximum at the end of the 24-finding was that the paclitaxel levels increased in the postinfusion CSF up to a maximum on Day 3 and then dehour infusion, which is similar to results published in Phase I studies. 1,9 clined, which is consistent with a diffusion phenomena into and out of the CSF. Paclitaxel levels were also detected in malignant ascitic and pleural fluids with this Detection of Paclitaxel Levels in Human Cerebrospinal, method (Table 2).…”

Section: High Performance Liquid Chromatographysupporting

confidence: 59%

“…This curve shows the same S-shaped pattern as free paclimodification of previously described procedures. 1,11 To prepare samples for high pressure liquid chromataxel diluted first in ethanol and subsequently diluted into blocking buffer, and revealed an even greater sentography (HPLC) analysis, 0.5 mL of sera was combined with 1 mL acetonitrile, then centrifuged (for 10 sitivity in detecting drug levels. Complete inhibition of MoAb binding is seen again at a 1 mM concentration minutes at 10,000 RPM).…”

Section: Competitive Immunoradiometric Assaymentioning

confidence: 99%

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Development of two radioimmunoassays to detect paclitaxel in sera and in cerebrospinal, ascitic, and pleural fluids

Wang¹,

Schwartz²,

Regl³

et al. 1997

Cancer

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an immunoradiometric assay (IRMA), in which 125 I-labeled antibody was used, and in a more conventional tritiated radioimmunoassay (RIA),in which 3 H-paclitaxel Departments of Oncology and Molecular Pharwas used. macology, Montefiore Medical Center/Albert RESULTS. Both radioimmunoassays detected levels of paclitaxel in sera that were Einstein Cancer Center, Bronx, New York.comparable to those observed with HPLC. However, the IRMA was the most sensitive. Only the IRMA was able to detect low levels of paclitaxel in cerebrospinal fluid after paclitaxel infusion and in sera 3 weeks after infusion. Both the IRMA and RIA methods were able to detect paclitaxel in ascitic and pleural fluids. CONCLUSIONS.Monitoring paclitaxel levels reliably in sera and other bodily fluids is possible with these radioimmunoassays and may be of value in predicting and preventing toxicity and optimizing paclitaxel treatments.

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Section: High Performance Liquid Chromatographysupporting

confidence: 59%

Section: Competitive Immunoradiometric Assaymentioning

confidence: 99%

Development of two radioimmunoassays to detect paclitaxel in sera and in cerebrospinal, ascitic, and pleural fluids

Wang¹,

Schwartz²,

Regl³

et al. 1997

Cancer

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“…To further evaluate and expand drug sensitivity studies associated with HER-2/neu overexpression, we developed an in vivo chemotherapeutic drug sensitivity assay which utilized serial measurements Table 1 Eect of HER-2/neu overexpression on sensitivity of human breast cells to chemotherapeutic agents in vitro (Gormley et al, 1979) 5.6 (Robert et al, 1982) 1000 (MacMillan et al, 1978) 940 (Wiernik et al, 1987) 10.6 (Cohen et al, 1986) 400 (Nelson et al, 1980) 50…”

Section: Eect Of Her-2/neu Expression On Chemosensitivity Of Breast Amentioning

confidence: 99%

The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells

et al. 1997

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Recent studies indicate that oncogenes may be involved in determining the sensitivity of human cancers to chemotherapeutic agents. To de®ne the eect of HER-2/neu oncogene overexpression on sensitivity to chemotherapeutic drugs, a full-length, human HER-2/neu cDNA was introduced into human breast and ovarian cancer cells. In vitro dose-response curves following exposure to 7 dierent classes of chemotherapeutic agents were compared for HER-2-and control-transfected cells. Chemosensitivity was also tested in vivo for HER-2-and control-transfected human breast and ovarian cancer xenografts in athymic mice. These studies indicate that HER-2/neu overexpression was not sucient to induce intrinsic, pleomorphic drug resistance. Furthermore, changes in chemosensitivity pro®les resulting from HER-2/neu transfection observed in vitro were cell line speci®c. In vivo, HER-2/neu-overexpressing breast and ovarian cancer xenografts were responsive to dierent classes of chemotherapeutic drugs compared to control-treated xenografts with no statistically signi®cant dierences between HER-2/neu-overexpressing and nonoverexpressing xenografts. We found no instance in which HER-2/neu-overexpressing xenografts were rendered more sensitive to chemotherapeutic drugs in vivo. HER-2/neu-overexpressing xenografts consistently exhibited more rapid regrowth than control xenografts following initial response to chemotherapy suggesting that a high rate of tumor cell proliferation rather than intrinsic drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in human cancers.

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“…It has been reported that neuropathy associated with paclitaxel by a 24-h injection is dependent upon total cumulative dosage, and no known risk factors have been identified (Wiemik et al, 1987;Chaudhry et al, 1994). Little information is available on the pharmacokinetics and this toxicity.…”

mentioning

confidence: 99%

Neuromuscular toxicities of paclitaxel 210 mg m-2 by 3-hour infusion

Kunitoh

Saijo²,

Furuse³

et al. 1998

Br J Cancer

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Summary We retrospectively analysed neuromuscular toxicity associated with paclitaxel 210 mg m-2 given by 3-h infusion in 247 patients. The severity correlated significantly with total cumulative dose, but could not be predicted by the pretreatment clinical variables or by pharmacokinetic parameters. The toxicity tended to occur in early treatment cycles.Keywords: paclitaxel; peripheral neuropathy; myalgia; arthralgia; pharmacokinetics; risk factor Peripheral neuropathy and myalgia/arthralgia are among the significant toxicities of paclitaxel. It has been reported that neuropathy associated with paclitaxel by a 24-h injection is dependent upon total cumulative dosage, and no known risk factors have been identified (Wiemik et al, 1987;Chaudhry et al, 1994). Little information is available on the pharmacokinetics and this toxicity. There are also few reports of neuromuscular toxicity of the drug given by shorter infusion, the currently preferred method of administration (Gianni, 1995).The aim of this retrospective analysis was to evaluate the risk factors for neuromuscular toxicity associated with paclitaxel by a 3-h infusion. Pharmacodynamics were also analysed in patients in whom pharmacokinetic data were available. PATIENTS AND METHODSA retrospective analysis was performed on four phase II trials of paclitaxel at a dose of 210 mg m-2 given as a 3-h infusion. Two trials included patients with non-small-cell lung cancer, one trial patients with breast cancer and the other trial patients with ovarian cancer. A summary of the patient characteristics is given in Table 1.Paclitaxel was supplied by Bristol-Myers Squibb (Tokyo, Japan) as a solution containing 30 mg of the drug in 5 ml of 50% polyoxyethylated castor oil (Cremophor EL) and 50% dehydrated alcohol. Each patient received 210 mg m-2 paclitaxel diluted in 500 ml of 5% glucose in a 3-h i.v. infusion, every 3 weeks.Adverse reactions to paclitaxel were graded according to the toxicity criteria of the Japan Society for Cancer Therapy (Japan Society for Cancer Therapy, 1993).Pharmacokinetic analysis was performed during the first course of the treatment in 50 patients. Heparinized blood samples for the measurement of plasma paclitaxel concentration were collected before the infusion and at 5, 15 and 30 min, and 1, 2, 3, 4, 6, 12, 24 Spearman's correlation coefficient was used to determine the correlation between two variables. The difference in the grade of toxicity between the two groups was evaluated using the Mann-Whitney U-test. RESULTSThe median number of paclitaxel chemotherapy cycles was three (range 1-15), and the median cumulative dose of the drug was 630 mg m-2 (range 35-3150 mg m-2).Peripheral neuropathy was grade 0 in 51 (21%), grade I in 120 (49%), grade 2 in 64 (26%) and grade 3 in 12 (5%) patients; no patient suffered grade 4 neuropathy. The neuropathy was predominantly sensory, and only five patients (four with grade 2 and one with grade 3) experienced motor neuropathy. The severity of myalgia/arthralgia was grade 0 in 88 (36%), grade 1 in 74 (30%)...

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Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma.

Cited by 266 publications

References 12 publications

Development of two radioimmunoassays to detect paclitaxel in sera and in cerebrospinal, ascitic, and pleural fluids

Development of two radioimmunoassays to detect paclitaxel in sera and in cerebrospinal, ascitic, and pleural fluids

The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells

Neuromuscular toxicities of paclitaxel 210 mg m-2 by 3-hour infusion

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