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Objective: Paclitaxel is most commonly infused over 3 hs rather than the original schedule of 24 h as the briefer infusion duration results in greater convenience, similar efficacy, significantly less myelosuppression, and less cost. While differences in toxicity between 3- and 24-h infusions are well described, there is little information about the effect of modest prolongation of infusion duration, which is often employed in patients who develop hypersensitivity reactions. To assess whether prolonging a 3-h infusion significantly increases the degree of neutropenia, we reviewed our data from a randomized, crossover trial of 3-h versus 6-h versus 24-h regimens of paclitaxel., Methods: Results from 12 patients who were randomized to receive one 3-h, one 6-h and one 24-h infusion of paclitaxel in varied sequences during their first three cycles of treatment were analysed. The blood counts were monitored closely throughout each cycle of treatment., Results: Crossover trial methodology was used to assess the differences in the degree of neutropenia caused by the three different infusion regimens. The 24-h infusion regimen resulted in significantly worse neutropenia than the 3- or 6-h infusion regimens. There was no statistically significant difference between the 3- and 6-h infusion regimens with respect to all endpoints. The estimated mean difference in the duration of grade 3 or 4 neutropenia between the 3- and 6-h infusion regimens (6 h - 3-h) was 1.1 day (95% CI: -0.9, 3.2), and for grade 4 neutropenia, the estimated mean difference in the duration was 0.8 day (95% CI: -0.4, 2.0)., Conclusions: Increasing the duration of paclitaxel infusions from 3 to 6 h does not result in a statistically significant increase in the degree of neutropenia. Any additional neutropenia is likely to be of brief duration.

Purpose: To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life (QoL) in advanced non-small-cell lung cancer (NSCLC) compared with vinorelbine plus cisplatin as first-line chemotherapy., Patients and Methods: Patients (n = 1,218) with stage IIIB to IV NSCLC were randomly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks (DCb); or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks (VC)., Results: Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients (P =.044; hazard ratio, 1.183 [97.2% confidence interval, 0.989 to 1.416]). The 2-year survival rate was 21% for DC-treated patients and 14% for VC-treated patients. Overall response rate was 31.6% for DC-treated patients v 24.5% for VC-treated patients (P =.029). Median survival (9.4 v 9.9 months [for VC]; P =.657; hazard ratio, 1.048 [97.2 confidence interval, 0.877 to 1.253]) and response (23.9%) with DCb were similar to those results for VC. Neutropenia, thrombocytopenia, infection, and febrile neutropenia were similar with all three regimens. Grade 3 to 4 anemia, nausea, and vomiting were more common (P <.01) with VC than with DC or DCb. Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients, who experienced deterioration in QoL., Conclusion: DC resulted in a more favorable overall response and survival rate than VC. Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC. These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC.

Background: The objective of this phase I trial was to determine the maximally tolerated doses of the combination of docetaxel, epirubicin and cyclophosphamide., Patients and Methods: Patients with advanced cancer, World Health Organization (WHO) performance status 0 to 2, who had received up to one prior chemotherapy regimen were treated with docetaxel, epirubicin and cyclophosphamide repeated every 21 days. The cyclophosphamide dose was fixed at 600 mg/m(2) and the dose levels studied were: docetaxel/epirubicin; 60/60, 75/60, 75/75, 75/90, 85/90 and 85/105 mg/m(2). There was provision for the addition of prophylactic ciprofloxacin and granulocyte colony-stimulating factor (G-CSF) in separate steps if dose-limiting toxicity (DLT) was neutropenia related., Results: Forty-three patients were entered and all were assessable for toxicity. Dose-limiting toxicity, predominantly febrile neutropenia, was surprisingly seen at the first dose level. The addition of prophylactic ciprofloxacin did not permit dose escalation, but dose escalation was possible with the addition of G-CSF. The highest administered dose level with G-CSF was docetaxel 85 mg/m(2) and epirubicin 105 mg/m(2) with DLTs in five of six patients. Treatment was well tolerated in 10 patients treated at the recommended dose level (85/90) with only one patient experiencing DLT. Responses were seen in a range of malignancies including breast and anaplastic thyroid cancers. No significant pharmacokinetic interaction was observed, but a transient increase in epirubicinol plasma concentration occurred during and after docetaxel infusion., Conclusions: The recommended dose level of docetaxel 85 mg/m(2), epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) with G-CSF support has a favorable toxicity profile and is suitable for further investigation in phase II and III trials.

The combination of paclitaxel and etoposide was evaluated in a phase II study in patients with locally advanced or metastatic non small-cell lung cancer (NSCLC). Thirty-five patients, median age 61, received treatment with paclitaxel 200 mg/m (2) intravenous over 3 h on day 1, and oral etoposide, 100 mg daily on days 1-5. Cycles were repeated every 21 days for a maximum of nine cycles, or until progression occurred. Twenty-eight patients had stage IV disease, and seven patients had stage IIIA or B disease. There was one complete and seven partial responses (overall response rate, 23%). Two of these responses were in patients with stage III disease (29%) and six in patients with stage IV disease (21%). Median survival was 8.7 months, and 36% of patients were alive at 1 year. There were no treatment-related deaths and little grade 3 or 4 non-haematological toxicity although grade 3 or 4 neutropenia occurred in 60% of patients (33% of cycles). There were four episodes of febrile neutropenia. The combination of paclitaxel and oral etoposide is active in advanced NSCLC and can be delivered with acceptable toxicity.

Cisplatin-based chemotherapy is effective in non-small cell lung cancer (NSCLC), although it prolongs survival only modestly. Single-agent docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) is highly active against NSCLC. The activity and tolerability of two docetaxel/ cisplatin regimens were therefore investigated in two multicenter phase II studies, one in Australia and one in France. Chemotherapy-naive patients with inoperable NSCLC received either docetaxel 75 mg/m2 on day 1 plus cisplatin 75 mg/m2 3 weekly (n = 47; Australian study) or docetaxel 75 mg/m2 on day 1 plus cisplatin 100 mg/m2 every 3 weeks for three cycles then every 6 weeks (n = 51; French study). The majority of the population (74%) had metastatic disease. Seventy-eight patients were evaluable for efficacy. Overall response rates were 36% (95% confidence interval, 25 to 47) in all evaluable patients and 34% in patients with metastases. Median duration of response was 6 months, with a 4-month median time to progression. Median survival time was 9 months, with a 1-year survival rate of 34%. A median of four (range, one to nine) treatment cycles were administered. Febrile neutropenia occurred in 14% of patients. Severe infection, which occurred in less than 7% of patients, led to two toxic deaths. Other severe toxicities were rare, with severe stomatitis and severe neurosensory side effects reported in 2% and 1%, respectively, of treated patients. No severe fluid retention occurred. Docetaxel/cisplatin, administered as two different schedules, is well tolerated and exhibits efficacy in the range of the most established combinations in the treatment of advanced NSCLC.

For patients with metastatic breast cancer (MBC) who undergo high-dose therapy with autologous peripheral blood progenitor cell (PBPC) transplantation, an important prerequisite is a mobilization regimen that efficiently mobilizes PBPCs while producing an effective anti-tumor effect. We prospectively evaluated ifosfamide-based chemotherapy for mobilization efficiency, toxicity and disease response in 37 patients. Patients received two cycles of the ifosfamide-based regimen; ifosfamide (5 g/m2 with conventional-dose cycle and 6 g/m2 with mobilization cycle) with either 50 mg/m2 doxorubicin (if limited prior anthracycline and/or progression more than 12 months after an anthracycline-based regimen) or 175 mg/m2 paclitaxel. For the mobilization cycle, all patients received additional G-CSF (10 microg/kg SC, daily) commencing 24 h after completion of chemotherapy. The target yield was >6x10(6) CD34+ cells/kg, sufficient to support the subsequent three cycles of high-dose therapy. The mobilization therapy was well tolerated and the peak days for peripheral blood (PB) CD34+ cells were days 10-13 with no significant differences in the PB CD34+ cells mobilization kinetics between the ifosfamide-doxorubicin vs. ifosfamide-paclitaxel regimens. The median PBPC CD34+ cell content ranged from 2.9 to 4.0x10(6)/kg per day during days 9-14. After a median of 3 (range 1-5) collection days, the median total CD34+ cell, CFU-GM and MNC for all 44 individual sets of collections was 9.2x10(6)/kg (range 0.16-54.9), 37x10(4)/kg (range 5.7-247) and 7.3x10(8)/kg (range 2.1-26.1), respectively. The PBPC target yield was achieved in 35 of the 37 patients. The overall response rate for the 31 evaluable patients was 68% with 10% having progressive disease. Thirty-three patients have subsequently received high-dose therapy consisting of three planned cycles of high-dose ifosfamide, thiotepa and paclitaxel with each cycle supported with PBPCs. Rapid neutrophil and platelet recovery has been observed. Ifosfamide with G-CSF in combination with doxorubicin or paclitaxel achieves effective mobilization of PBPC and anti-tumor activity with minimal toxicity.

Docetaxel activity has been documented in many solid tumors, including metastatic breast cancer and non-small cell lung cancer. However, as clinical studies in other tumor types are now being conducted, the validation of an optimal sampling strategy would allow the performance of pharmacokinetics/pharmacodynamics studies with minimum inconvenience for the patient. Six optimal sampling strategies with one to six sampling times were computed, based on the D-optimality theory, using population pharmacokinetic parameters estimated from a large pharmacokinetic database of 547 patients treated in previous Phase II studies. Validation of these sampling strategies was performed on a set of 35 patients, from two Phase I studies, who received docetaxel as a 1-h infusion at doses ranging from 50 to 100 mg/m2. Validation consisted of comparing clearance assessed by maximum likelihood estimation obtained using complete plasma concentration-time data (considered as the reference) and clearance determined by Bayesian estimation with an optimal design. For all of the optimal sampling strategies tested, clearance was found to be well estimated when at least two samples were taken. Bayesian estimation with two measured levels (at the end of infusion and at 6 h after the start of infusion) can be selected, because it allows adequate estimation of clearance with a nonsignificant bias of +1.37% and a precision of 12.3%.

Background: Metastatic breast cancer is a major cause of cancer death in Australian women. Docetaxel is a new cytotoxic drug that has shown promise in the treatment of metastatic breast cancer in patients who have previously received other chemotherapy, particularly an anthracycline, and has recently been approved for marketing in Australia., Aim: To report the first Australian experience with docetaxel in a group of women with metastatic breast cancer., Methods: Patients with progressive metastatic breast cancer who had previously received other chemotherapy were treated with docetaxel 75 mg/m2 or 100 mg/m2 given as a one hour infusion every three weeks. All patients received oral dexamethasone for five days starting 24 hours prior to docetaxel as prophylaxis against fluid retention. The patients' response to docetaxel and toxicity were assessed by standard criteria., Results: Twenty-six patients were treated. The major toxicity was neutropenia with 92% of patients experiencing at least one episode of grade 4 (absolute neutrophil count < 0.5 x 10(9)/L) neutropenia. Hospital admission for febrile neutropenia occurred in 44% of patients with one death from sepsis. Cumulative fluid retention was observed but in only one patient was it dose-limiting. Apart from alopecia, other toxicities were infrequent and rarely serious. In 23 patients assessable for response, there were 11 partial responses (48%). Three other patients whose disease could not be assessed for response had clinical improvement. The median survival of all patients treated was eight months., Conclusions: The response rate observed with docetaxel is comparable to that seen in trials in the United States and Europe and confirms the high activity of this new cytotoxic agent. Neutropenia is the major toxicity, and consideration should be given to the use of prophylactic oral antibiotics or colony stimulating factors to try and prevent febrile episodes. Clinicians will need to balance the benefits, toxicities, and cost of docetaxel in determining the appropriateness of its use in their patients.

Docetaxel (Taxotere, Rhone-Poulenc Rorer) and etoposide are water-insoluble drugs formulated with polysorbate 80 for intravenous administration. We have previously reported that surfactants, including polysorbate 80 and Cremophor EL, can reverse the multidrug resistance (MDR) phenotype in an experimental system and that plasma Cremophor EL concentrations measured following a 3-h infusion of paclitaxel were > or = 1 microliter/ml, sufficient to modulate MDR in vitro. The purpose of this study was to measure polysorbate 80 plasma concentrations in patients following intravenous administration of etoposide or docetaxel using a bioassay in which MDR-expressing cells are incubated with daunorubicin (DNR) plus 50/50 growth medium/plasma and equilibrium intracellular DNR fluorescence is measured by flow cytometry. In vitro experiments show maximal reversal of MDR at concentrations of 1.0-2.0 microliters/ml and 50% reversal at 0.2-0.3 microliter/ml. Patients received docetaxel at 75 mg/m2 (five patients) or 100 mg/m2 (four patients) (total dose 125-178 mg, containing 3.12-4.45 ml polysorbate 80) over 60 min. The median end-infusion polysorbate 80 concentration was 0.1 microliter/ml (range 0.07-0.41 microliter/ml). Only one patient had a level of > 0.2 microliter/ml. Five patients received intravenous etoposide at 120 mg/m2 over 45-120 min (total dose 180-250 mg, containing 0.67-0.93 ml polysorbate 80). In the end-infusion plasma sample, polysorbate 80 was not detectable (< 0.06 microliter/ml) in any patient. Plasma polysorbate 80 levels following an intravenous infusion of 120 mg/m2 etoposide or of docetaxel at doses used in Phase II trials, are insufficient to show modulation of MDR in vitro.

Thirty-eight women with epithelial ovarian cancer were treated with gemcitabine, a new antimetabolite. All had previously received platinum, and 27 had also received paclitaxel. Four patients had a partial response giving a response rate of 13% in assessable patients (n = 31) and 11% for all patients entered. Additionally, 6 patients had stable disease with >50% reduction in CA-125 for at least 3 months. Activity was seen in patients resistant to both platinum and paclitaxel. Gemcitabine was well tolerated, with uncomplicated neutropenia the main hematological toxicity. Nonhematological toxicities were generally mild and included fatigue, myalgias, and skin rash. Gemcitabine has some activity in heavily pretreated ovarian cancer patients and deserves further investigation in this malignancy.

Background: Paclitaxel (Taxol) is a new drug with efficacy against a variety of malignant tumors. The clinical formulation of paclitaxel contains 50% Cremophor EL, a polyethoxylated castor oil vehicle (carrier) that can reverse multidrug resistance (MDR) mediated by P-glycoprotein. Three-hour intravenous infusions of paclitaxel can yield end-of-infusion plasma Cremophor concentrations of 1 microL/mL or more, which are sufficient to reverse MDR in vitro by at least 50%. Despite extensive clinical use, the pharmacokinetics of Cremophor have not been described., Purpose: We studied the pharmacokinetics of Cremophor in patients with ovarian cancer who were undergoing treatment with paclitaxel to determine whether plasma Cremophor concentrations achieved during and following 3-, 6-, and 24-hour drug infusions were similar to those shown to modulate MDR in vitro., Methods: Eleven patients with previously treated (i.e., with platinum-containing chemotherapy regimens) ovarian cancer were randomly assigned to receive one 3-hour, one 6-hour, and one 24-hour infusion of paclitaxel in varied sequences during their first three cycles of treatment with this drug. Blood samples were collected both during and following the three infusion periods, and Cremophor concentrations in these samples were measured by use of a bioassay based on the ability of Cremophor in plasma samples to reverse cellular resistance to daunorubicin in vitro., Results: Ten patients were treated with paclitaxel at a dose level of 175 mg/m2, and one patient was treated at a dose level of 135 mg/m2. At the 175-mg/m2 dose level, peak plasma Cremophor concentrations of 1 microL/mL or more were achieved in eight of 10 patients during both the 3-hour and the 6-hour infusions; with the 24-hour infusion, only one patient achieved a peak plasma Cremophor concentration of 1 microL/mL or more. The eight patients who achieved plasma Cremophor concentrations of 1 microL/mL during the 3-hour infusion were above this level 30 minutes into the infusion; the total time that the plasma concentration was greater than 1 microL/mL was 8.9 +/- 5.0 hours (mean +/- standard deviation; range, 4.1-15.6 hours). For the eight patients who achieved plasma Cremophor concentrations of 1 microL/mL during the 6-hour infusion, the total time that the concentration was greater than 1 microL/mL was 10.2 +/- 9.0 hours (range, 0.3-21.9 hours). The patient who received paclitaxel at a dose of 135 mg/m2 achieved a peak plasma Cremophor concentration of 1 microL/mL or more only during the 3-hour infusion., Conclusions: Paclitaxel infusions of 3 and 6 hours can result in sustained plasma Cremophor concentrations sufficient for substantial reversal of P-glycoprotein-mediated MDR in vitro. These plasma Cremophor concentrations are not achieved during 24-hour infusions of paclitaxel.

We describe the occurrence of acquired Pelger-Huet anomaly (APHA) in 23 patients treated with paclitaxel (13) or docetaxel (10). A consistent peak of Pelger-Huet cells (PHC) within a range of 3-9 d after treatment with taxoids was noted. The APHA generally disappeared by day 21 after treatment. Peak PHC values for the first course were significantly different in paclitaxel versus docetaxel versus control groups (P < 0.0001) with the maximum PHC counts being significantly higher for docetaxel compared with paclitaxel (P < 0.001) and for paclitaxel compared with controls (P = 0.007). We conclude that taxoid therapy produces transient APHA which peaks between days 3 and 9 and is more pronounced with docetaxel than with paclitaxel.

Paclitaxel is formulated in 50% Cremophor El and 50% ethanol such that patients receiving paclitaxel also receive a significant amount of each of these solvents. The aim of this study was to measure the plasma alcohol levels in patients treated with paclitaxel. A total of 12 patients who were enrolled in phase II trials of non-small-cell lung cancer, breast cancer or ovarian cancer received 175 mg/m2 paclitaxel given as a 3-h infusion. Blood samples were obtained prior to and immediately following the infusion, and plasma ethanol concentrations were measured enzymatically. The dose of ethanol delivered with the paclitaxel ranged from 20.0 to 28.9 ml. No alcohol was detected in pre-dose plasma, but 8 of 12 patients had detectable levels in post-infusion plasma, with 0.033 g/dl being the highest concentration. The elimination rate of alcohol approximates the infusion rate when paclitaxel is given over 3h, resulting in low or undetectable levels in most patients. However, in patients receiving an equivalent dose of paclitaxel given as a 1-h infusion, the plasma alcohol levels will likely be high enough for significant pharmacological effects to occur.

Purpose: To determine the antitumor activity and toxicity of paclitaxel administered as a 3-hour infusion in patients with advanced non-small-cell lung cancer (NSCLC)., Patients and Methods: Fifty-one patients with advanced measurable or assessable NSCLC and performance status 0 to 2 who had not received prior chemotherapy were treated with paclitaxel 175 mg/m2 over 3 hours with premedication. Cycles were repeated every 3 weeks for a maximum of nine cycles. Most patients had prior radiotherapy (57%), extrathoracic metastatic disease (65%), and measurable disease (75%). Twenty-two percent had previously untreated stage III disease., Results: The objective response rate was five of 51 (10%; 95% confidence interval, 3% to 21%). No subgroup with a higher response rate could be identified. There were no complete responses (CRs) and all responses lasted less than 5 months. Treatment was well tolerated with brief World Health Organization (WHO) grade IV neutropenia in only 16% of patients. Grade III/IV myalgia/athralgia occurred in 22% of patients. No significant hypersensitivity reactions occurred., Conclusion: The antitumor activity of this dose and schedule appears inferior to that reported in previously published phase II trials in NSCLC that used higher doses of paclitaxel infused over 24 hours, although confidence intervals for response overlap. Determining the optimal dose and schedule for using paclitaxel in NSCLC requires further investigation, and these results should caution against using shorter infusions outside appropriate clinical trials.

Background: Paclitaxel (Taxol) is the first of a new class of cytotoxic agents with activity against tumors resistant to other drugs. For clinical use, paclitaxel is currently formulated in a vehicle of 50% ethanol and 50% polyethoxylated surfactant Cremophor EL (Cremophor). We have previously shown that Cremophor will block the P-glycoprotein drug efflux pump responsible for the multidrug-resistant phenotype. Overexpression of P-glycoprotein is one mechanism of in vitro resistance to a number of currently used cytotoxic agents including paclitaxel., Purpose: Our aim was to develop a bioassay to measure plasma levels of Cremophor and to determine whether or not plasma levels of Cremophor achieved during paclitaxel therapy are sufficient to inhibit the activity of the P-glycoprotein., Methods: All patients studied had histologically proven, advanced ovarian carcinoma with measurable or evaluable disease and had received at least one prior platinum-containing regimen. The bioassay used flow cytometry to measure the increase in equilibrium intracellular daunorubicin levels in multidrug-resistant human T-cell leukemia cells (CEM/VLB100) in the presence of a series of concentrations of Cremophor. Levels of Cremophor were measured in plasma from 21 patients after a 3-hour infusion of 135 or 175 mg/m2 paclitaxel. Both dose levels were given following premedication with oral dexamethasone, intravenous promethazine hydrochloride, and intravenous cimetidine. The Cremophor bioassay involved incubation of CEM/VLB100 cells (5 x 10(5)) for 1 hour with 2 micrograms/mL daunorubicin in 0.5 mL HL-1 medium plus 0.5 mL plasma prior to flow cytometric analysis. Pretreatment plasma was used to derive a standard curve for the effect of Cremophor on equilibrium daunorubicin levels. All measurements were done in triplicate., Results: In vitro experiments indicated that, for maximal inhibition of P-glycoprotein activity, concentrations of Cremophor of 0.1% (vol/vol) were required. At the end of a 3-hour infusion of paclitaxel, plasma levels of Cremophor in 19 of 21 patients were 0.1% or higher and 0.09% in the remaining two. Concentrations of 5-20 microM paclitaxel dissolved in ethanol without Cremophor did not inhibit P-glycoprotein in this assay., Conclusion: The concentrations of Cremophor measured in plasma drawn from patients after a 3-hour infusion of paclitaxel at 135 or 175 mg/m2 were found to be sufficient to inhibit P-glycoprotein activity in vitro., Implications: The efficacy of paclitaxel against some tumors may be aided by its administration in a vehicle solution containing Cremophor in quantities that reach concentrations in the plasma sufficient to reverse multidrug resistance of neoplastic cells.

Initial trials of paclitaxel and doxorubicin in advanced breast cancer yielded high response rates but significant cardiac toxicity was observed. In this phase II trial we investigated the efficacy and safety of paclitaxel combined with epirubicin. Patients with advanced breast cancer, performance status 0-2, measurable disease, and a normal left ventricular ejection fraction, who may have received adjuvant chemotherapy were treated with epirubicin 75 mg m[SUP-2]followed by a 3-h infusion of paclitaxel 175 mg m[SUP-2] repeated every 3 weeks. Forty-three eligible patients were treated at six centres. 67% patients received the maximum of six cycles. The response rate was 54% (95% CI 38-69%), 12% CR and 42% PR. Estimated median progression-free survival was 6.9 months (95% CI 5.4-10.0) and estimated median overall survival was 17.9 months (95% CI 14.2-25.7). Four patients had a decrease in the left ventricular ejection fraction (LVEF) of ≤20% of baseline value, and in two patients the LVEF decreased to below the lower limit of normal, but no patient developed clinical evidence of cardiac failure. Grade 4 neutropenia occurred in 56% cycles, but only 4% of cycles were complicated by febrile neutropenia. Grade 3 or 4 non-haematologic toxicity was uncommon. In conclusion, paclitaxel 175 mg m[SUP-2]and epirubicin 75 mg m[SUP-2]is a well tolerated, promising regimen for the treatment of advanced breast cancer. [ABSTRACT FROM AUTHOR]

The optimal chemoradiation regimen for stage III non-small cell lung cancer (NSCLC) has not been determined. In this phase I/II study, the use of twice-weekly paclitaxel concomitant with weekly cisplatin and thoracic radiotherapy (RT) was evaluated. Patients with stage III NSCLC (without pleural effusion or cervical lymphadenopathy) were treated with thoracic RT (60 Gy in 30 fractions over 6 weeks) with concurrent weekly cisplatin 20 mg/m2 and escalating doses of twice-weekly paclitaxel (starting dose of paclitaxel of 20 mg/m2 increased in increments of 5 mg/m2) in successive cohorts of three to six patients until two or more patients experienced dose limiting toxicities (DLTs) at a particular dose level. All patients were planned to be given a further two cycles of consolidation chemotherapy consisting of paclitaxel 175 mg/m2 and carboplatin AUC 5 after completion of RT. Twenty-five patients were enrolled in this study from two institutions. At a dose of paclitaxel 35 mg/m2, two of four treated patients had DLTs (1 grade 3 oesophagitis and pulmonary toxicity; 1 grade 3 oesophagitis and infection). The recommended dose was therefore determined to be 30 mg/m2 and a total of 15 patients were enrolled in an expanded cohort at this level. The overall response rate for all patients was 64% (95% CI: 43–82%). The estimated median survival was 23.6 months with an estimated 1-year and 2-year survival of 72 and 49%, respectively. Paclitaxel can be safely given twice-weekly at a dose of 30 mg/m2 in combination with weekly cisplatin (20 mg/m2) and thoracic RT (60 Gy), and this regimen has significant activity in stage III NSCLC. [Copyright &y& Elsevier]