Weekly Paclitaxel in Elderly Patients (Aged ≥ 70 Years) with Advanced Non–Small-Cell Lung Cancer: An Alternative Choice? Results of a Phase II Study

Rossi, David; Dennetta, Donatella; Ugolini, Marcello; Alessandroni, Paolo; Catalano, Vincenzo; Fedeli, Stefano; Giordani, Paolo; Casadei, Virginia; Baldelli, Anna Maria; Graziano, Francesco; Catalano, Giuseppina

doi:10.3816/clc.2008.n.043

Cited by 17 publications

(8 citation statements)

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“…The activity and safety of weekly paclitaxel as a single agent have been assessed in several phase II trials [ 10 , 13 , 14 , 16 – 27 ]. In most cases, the administered dose was 80 mg/m 2 [ 13 , 14 , 16 – 19 , 21 , 22 ], and doses of 90 mg/m 2 [ 10 ] or 100 mg/m 2 [ 20 ] are rarely reported. The objective response rate ranged from 8% [ 17 , 22 ] to 38% [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…This inhibition of de-polymerization is observed during the metaphase/anaphase transition of mitosis [ 5 ]. Paclitaxel exhibits a wide spectrum of anti-tumor activity, including breast cancers, even those refractory to anthracyclines; lung cancers; squamous cell carcinomas of the upper respiratory/digestive tracts; stem cell tumors; lymphomas; and Kaposi tumors [ 6 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Once weekly paclitaxel associated with a fixed dose of oral metronomic cyclophosphamide: a dose-finding phase 1 trial

et al. 2018

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BackgroundThe primary aim of this trial was to determine the recommended phase II dose (RP2D) of weekly paclitaxel (wP) administered in combination with oral metronomic cyclophosphamide (OMC).MethodsPatients ≥ 18 years of age with refractory metastatic cancers were eligible if no standard curative measures existed. Paclitaxel was administered IV weekly (D1, D8, D15; D1 = D28) in combination with a fixed dose of OMC (50 mg twice a day). A 3 + 3 design was used for dose escalation of wP (40 to 75 mg/m2) followed by an expansion cohort at RP2D. Dose-limiting toxicity (DLT) was defined over the first 28-day cycle as grade ≥ 3 non-hematological or grade 4 hematological toxicity (NCI-CTCAE v4.0) or any toxicity leading to a dose reduction.ResultsIn total, 28 pts. (18 in dose-escalation phase and 10 in expansion cohort) were included, and 16/18 pts. enrolled in the dose-escalation phase were evaluable for DLT. DLT occurred in 0/3, 1/6 (neuropathy), 0/3 and 2/4 pts. (hematological toxicity) at doses of 40, 60, 70 and 75 mg/m2 of wP, respectively. The RP2D of wP was 70 mg/m2; 1/10 patients in the expansion phase had a hematological DLT. At RP2D (n = 14), the maximal grade of drug-related adverse event was Gr1 in three patients, Gr2 in six patients, Gr3 in one patient and Gr4 in one patient (no AE in three patients). At RP2D, a partial response was observed in one patient with lung adenocarcinoma.ConclusionThe combination of OMC and wP resulted in an acceptable safety profile, warranting further clinical evaluation.Trial registrationTRN: NCT01374620; date of registration: 16 June 2011.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4678-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Once weekly paclitaxel associated with a fixed dose of oral metronomic cyclophosphamide: a dose-finding phase 1 trial

et al. 2018

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“…9 Furthermore, weekly paclitaxel, either as combined or monotherapy, has been considered an active and feasible option in elderly patients in Phase II trials. 13,14 Limited studies exist on weekly paclitaxel in Japanese patients with advanced NSCLC. 13,15,16 Despite premedication with dexamethasone and H 1 /H 2 blockers, severe hypersensitivity reactions occur in 2% to 4% of patients receiving 3-weekly paclitaxel.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Weekly Paclitaxel and Feasibility of Dexamethasone Taper in Japanese Patients with Advanced Non–small Cell Lung Cancer

Nokihara¹,

Yamamoto²,

Ohe³

et al. 2016

Clinical Therapeutics

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“…Taxol (paclitaxel) is one of the most active cancer chemotherapeutic agents known and is effective against several human malignancies, including ovarian, breast, and non-small cell lung cancer (NSCLC) [18–23]. Taxol promotes microtubule (MT) assembly, which produces a change in MT dynamics that disrupts the reorganization of the microtubule network required for mitosis and cell proliferation [24].…”

Section: Introductionmentioning

confidence: 99%

Human β-galactoside α-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 activity

et al. 2009

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Taxol triggers apoptosis in a variety of cancer cells, but it also upregulates cytoprotective proteins and/or pathways that compromise its therapeutic efficacy. In this report, we found that Taxol treatment resulted in caspase-8-dependent apoptosis in SKOV3 human ovarian cancer cells. Moreover, Taxol-induced apoptosis was associated with caspase-3 activation. Interestingly, Taxol treatment upregulated α-2,3-sialyltransferase (ST3Gal III) expression and forced expression of ST3Gal III attenuated Taxol-induced apoptosis. Furthermore, ST3Gal III overexpression inhibited Taxol-ttiggered caspase-8 activation, indicating that ST3Gal III upregulation produces cellular resistance to Taxol and hence reduces the efficacy of Taxol therapy.

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Weekly Paclitaxel in Elderly Patients (Aged ≥ 70 Years) with Advanced Non–Small-Cell Lung Cancer: An Alternative Choice? Results of a Phase II Study

Cited by 17 publications

References 15 publications

Once weekly paclitaxel associated with a fixed dose of oral metronomic cyclophosphamide: a dose-finding phase 1 trial

Once weekly paclitaxel associated with a fixed dose of oral metronomic cyclophosphamide: a dose-finding phase 1 trial

Pharmacokinetics of Weekly Paclitaxel and Feasibility of Dexamethasone Taper in Japanese Patients with Advanced Non–small Cell Lung Cancer

Human β-galactoside α-2,3-sialyltransferase (ST3Gal III) attenuated Taxol-induced apoptosis in ovarian cancer cells by downregulating caspase-8 activity

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