Docetaxel and Cisplatin in Patients with Advanced Non–Small-Cell Lung Cancer (NSCLC): A Multicenter Phase II Trial

original contribution Docetaxel and Cisplatin in Patients with Advanced Non–Small-Cell Lung Cancer (NSCLC): A Multicenter Phase II Trial Chandra P. Belani1, Philip Bonomi2, Tracey W. Dobbs3, Russell F. DeVore4, David S. Ettinger5, James Jett1, James D. Luketich1, Lewis J. Cohen6, David H. Johnson4 Abstract We examined the safety and efficacy of the docetaxel/cisplatin combination in patients with advanced, previously untreated NSCLC and evaluated changes in quality of life over time. Docetaxel was administered before cisplatin (both 75 mg/m2, 1-hour infusions) every 3 weeks to 47 patients with stage IIIB or stage IV NSCLC. Patients also received premedication of oral dexamethasone. The median age (range) of patients was 62 (45-78) years and 26 patients (55.3%) had adenocarcinoma. Of the 40 patients evaluable for response, one achieved a complete response and 14 had partial responses; the response rate was 37.5% (95% confidence intervals; 22.5, 52.5). In the intent-to-treat population the overall response rate was 31.9%. Time to response ranged from 3 to 20 weeks, and the median duration of response was 34.6 weeks. Median survival and median time to progression were 11.3 months and 18.9 weeks, respectively. One-year survival was 40%. Grade 3 or 4 neutropenia and febrile neutropenia were observed in 74.4% and 12.8% of patients, respectively. Severe asthenia was seen in 14.9% of patients. Other grade 3 or 4 toxicities included nausea (eight patients), vomiting (five), neurosensory effects (six), neuromotor effects (five), diarrhea (four), and infection (three). There was an improvement in emotional well-being; however, the overall quality of life score did not change with treatment. Docetaxel administered in combination with cisplatin is an active regimen in patients with NSCLC. This regimen of docetaxel (75 mg/m2) and cisplatin (75 mg/m2) repeated at 3-week intervals is being evaluated in an ongoing Eastern Cooperative Oncology Group (ECOG) randomized study in patients with advanced and metastatic NSCLC. Clinical Lung Cancer, Vol. 1, No. 2, 144-150, 1999

Key words: Docetaxel, Cisplatin, Non–small-cell lung cancer

Introduction

of approximately 20%-25%.2,3 In addition, improvements in disease-related symptoms and overall quality of life have been observed.3,4 Regimens employing cisplatin in combinations with new agents such as paclitaxel, vinorelbine, gemcitabine, and irinotecan have improved overall outcome of patients with advanced and metastatic disease to 25%-40%.5-9 Docetaxel has also proved to be efficacious in NSCLC.10-14 In four phase II studies involving 160 chemo-naive patients with advanced NSCLC, docetaxel was administered as 100 mg/m2 in a 1-hour intravenous infusion every 3 weeks. Of the 141 patients evaluable for response, 31% had an objective response.10-12,14 Median duration of response, median time to progression, and median survival were 6 months, 3 months, and 9.2 months, respectively.15 The 1-year survival rate was 39%.15 Docetaxel monotherapy has also been evaluated in a total of 88 patients with advanced or metastatic platinumrefractory NSCLC. Of the 71 evaluable patients, 17% achieved an objective response. 16 The median duration of response was 29 weeks and the median survival was 9 months.

Non–small-cell lung cancer (NSCLC), which includes squamous cell carcinoma, large cell carcinoma, anaplastic carcinoma, and adenocarcinoma, accounts for approximately 75% of all lung cancer cases.1 Surgical resection alone is the treatment of choice in patients with early stage disease. Cisplatinbased chemotherapy combinations improve survival of patients with advanced or metastatic disease from 5 months (with best supportive care) to 8 months, with 1-year survival 1University of Pittsburgh Cancer Institute, Pittsburgh, PA 2Rush-Presbyterian Medical Center, Chicago, IL 3Baptist Medical Center, Knoxville, TN 4Vanderbilt University Medical Center, Nashville, TN 5Johns Hopkins Medical Center, Baltimore, MD 6Rhône-Poulenc Rorer Pharmaceuticals Inc., Collegeville, PA

Submitted: Aug. 30, 1999; Revised: Oct. 25, 1999; Accepted: Oct. 26, 1999 Address for correspondence: Chandra P. Belani, MD, University of Pittsburgh Cancer Institute, 200 Lothrop Street, MUH N-725, Pittsburgh, PA 15213 Fax: 412-648-6579; e-mail: [email protected]

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The main side effects of docetaxel monotherapy were neutropenia, hypersensitivity, sensory neuropathy, and fluid retention.10-13 The rationale for combining docetaxel and cisplatin is based on their activity as single agents in NSCLC, their nonoverlapping toxicity profiles, and the lack of cross-resistance.17,18 To establish the maximally tolerated doses, the combination of docetaxel and cisplatin was initially studied in a phase I trial of 25 chemo-naive patients with unresectable NSCLC. 19 Docetaxel doses ranged from 75 to 85 mg/m2 every 3 weeks and cisplatin ranged from 75 to 100 mg/m2 given on days 1 and 22 and then every 6 weeks. Dose-limiting toxicity was febrile neutropenia, which was observed in 45% of patients. Bishop et al 20 also conducted a phase I study of the combination of docetaxel and cisplatin in previously untreated patients with NSCLC. At the highest dose level, docetaxel (100 mg/m2) combined with cisplatin (75 mg/m2), 2 patients experienced unacceptable toxicity. It was concluded that 75 mg/m 2 of docetaxel and 75 mg/m 2 of cisplatin were the recommended doses for this combination. The purpose of this study is to evaluate the effect of docetaxel (75 mg/m2) in combination with cisplatin (75 mg/m2) on response rate, time to progression, survival, safety, and quality of life in previously untreated, chemo-naive patients with advanced and metastatic NSCLC.

Materials and Methods Patients were eligible for inclusion if they were aged > 18 years and had microscopically or cytologically confirmed inoperable stage IIIB or stage IV non–small-cell lung cancer, an ECOG status of 0 or 1, and at least one bidimensionally measurable indicator lesion that had not been irradiated. In addition, patients had to have adequate bone marrow function (absolute neutrophil count [ANC] ≥ 1500 cells/mm3, platelet count ≥ 100,000 cells/mm3, hemoglobin ≥ 10 g/dL), adequate kidney function (creatinine ≤ 1.5 mg/dL, creatinine clearance > 65 mL/minute), and adequate liver function (normal total bilirubin, alkaline phosphatase ≤ 5 x upper limit of normal [ULN], serum glutamate oxalate transaminase [SGOT] ≤ 1.5 x ULN). Exclusion criteria included prior systemic chemotherapy or immunotherapy; peripheral neuropathy ≥ National Cancer Institute (NCI) grade 2; metastatic central nervous system disease; pregnancy and lactation; malignancy within the last 5 years that could have affected the diagnosis of NSCLC; concurrent steroid use (except as chronic treatment > 6 months at doses of 20 mg methylprednisolone or equivalent); and prior major surgery or radiation therapy to the pelvis, spine, or long bones within 4 weeks of the start of the trial. The protocol was approved by the Institutional Review Boards (IRB) of the participating centers, and written, informed consent was obtained from all patients.

Treatment Plan Patients received 75 mg/m 2 docetaxel (Rhône-Poulenc

Rorer Pharmaceuticals, Collegeville, PA) intravenously over 1 hour followed by 75 mg/m2 cisplatin intravenously over 1 hour. All patients were pretreated with 8 mg dexamethasone orally twice daily for 5 days beginning the day before study drug infusions. Anti-emetic treatment and hydration therapies were administered to patients at the discretion of the investigator. Docetaxel/cisplatin treatment was repeated every 21 days until there was evidence of progressive disease or unacceptable side effects. Patients were discontinued from treatment if they had ≥ grade 3 neurotoxicity or ≥ grade 2 diarrhea despite prophylactic treatment. Dose reductions were defined for hematologic toxicities and most nonhematologic toxicities. Patients experiencing grade 4 thrombocytopenia had their docetaxel dose reduced by 25% at the next cycle, whereas patients experiencing grade 4 neutropenia or leukopenia that lasted for ≥ 7 days, or was combined with fever initially, resumed treatment at the original dose but with the addition of prophylactic granulocyte colony-stimulating factor (G–CSF). If there was a subsequent recurrence of symptoms, the dose of docetaxel was reduced by 25%. Patients experiencing abnormal liver function tests or grade 3 or 4 cutaneous toxicity had their docetaxel dose reduced by 25%. A maximum of two 25% dose reductions for docetaxel was allowed per patient (from 75 mg/m2 to 55 mg/m2 and from 55 mg/m2 to 40 mg/m2). Dose reductions were not made for hypersensitivity reactions or fluid retention. Patients with grade 2 neurotoxicity, or any other grade 3 or 4 toxicity not already mentioned (excluding alopecia or anemia), had a 25% dose reduction of both docetaxel and cisplatin.

Study Evaluations A complete medical history and physical examination, including a neurologic evaluation, were performed at baseline. Physical examinations were also performed at the end of each cycle and at the end of the study. Biochemical and hematologic assessments were performed at baseline, at the end of each cycle, and at the end of the study. Patients had a complete blood count and differential count weekly during the first 2 cycles and then once every cycle thereafter. Arterial blood pressure, pulse rate, and respiratory rate were measured before administration of docetaxel, every 15 minutes during administration, and 2 hours after administration. Objective disease assessments using computed tomography (CT), ultrasound, or chest x-rays were performed every 2 cycles. Tumor response was evaluated using the same method at each assessment. Bone, liver, and abdominal CT scans were performed every other cycle if they were positive at baseline; otherwise, they were done if clinically indicated. Responses were graded by standard criteria (complete response, partial response, stable disease, and progressive disease) by the investigator. Complete response (CR) was defined as the disappearance of all clinical, radiologic, and biochemical evidence of disease for at least 4 weeks. Partial response (PR) was defined as a reduction in the product of two diameters of measurable disease by at least 50% for at least 4 weeks. Stable

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DocetaxeVCisplatinininPatients Patientswith withLung LungCancer Cancer Docetaxel/Cisplatin values. Confidence intervals were calculated at the 950/0 level. Duration. of response was calculated from the day that the complete response or partial response criteria were first met until the day of documented disease progression. The time to progression was calculated from the time of the first docetaxel infusion to the first objective evidence of tumor progression. Survival time was calculated by Kaplan-Meier estimation. Internal consistency of the FACT-L was assessed by Cronbach's coefficient alpha, a widely used measure of reliability that is an indicator of the interrelatedness of a set of items. Paired t-tests were used to assess the statistical significance between baseline and treatment FACT-L scores.

Results Results A total of 47 patients with stage IIIB or stage IV NSCLC were enrolled in the study by five investigators between February 24, 1995, and March 13, 1996 (Table 1). The majority of patients in the intent-to-treat population were male (57.4%), aged between 45 and 78 years (median age of 62 years), with an ECOG performance status of 1 (76.60/0). The most common histologic subtype was adenocarcinoma (55.3%). Three patients (6.4%) were classified as having locally advanced disease (stage IIIB) and 44 patients (93.60/0) had metastatic disease (stage IV). Twenty-six patients (55.30/0) had received no prior cancer treatment. One patient had received prior chemotherapy and was not available for tumor and follow-up assessments.

Treatment

*

NOS: not otherwise specified.

disease was defined as objective regression of measurable disease less than that required to meet criteria for PR and no disease progression for at least 8 weeks. Progression of disease was defined as an increase by 250/0 or more in the sum of the products of the two greatest perpendicular diameters of any measurable lesion. Adverse events were recorded and classified according to the National Cancer Institute (NCI) common toxicity criteria. Other toxic effects were graded as mild (asymptomatic or minor symptoms; no treatment required), moderate (moderately symptomatic; minor treatment required), or severe (symptomatic and interfering with function; major treatment required). Quality of life was measured with the modified Functional Assessment of Cancer Therapy-Lung (FACT-L) instrument.U The modified FACT-L consists of the FACT-L and the taxane toxicity subscale. The modified FACT-L was completed by patients ~ 7 days prior to cycle 1, on day 1 of cycles 3 and 5, and at week 26 prior to the administration of the study drug. Once the patient went off treatment, the modified FACT-L was completed at 6 weeks, 12 weeks, and 26 weeks after initiation of therapy.

Statistical Approach Continuous data were summarized using descriptive statistics including mean, median, minimum, and maximum

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The 47 patients received a total of 237 cycles of treatment. The median number of cycles administered was 5 (range, 1 to 11). The planned dosage regimen of docetaxel 75 mg/m 2 and cisplatin 75 rng/rn- was administered in 205 cycles. A dose reduction was necessary in 17 docetaxel cycles and 15 cisplatin cycles. Overall, the median cumulative dose was 361 mg/rn(range, 1 to 734 mg/m 2) for docetaxel and 374 rng/rn- (range, o to 662 mg/rn-) for cisplatin.

Response In the intent-to-treat population of 47 patients, the overall objective response rate was 31.90/0 (950/0 CI; 18.6, 45.2) (Table 2). Of these 47 treated patients, 40 patients were

Chandra P. Belani et al Table 3

Hematologic and Nonhematologic Toxicity

Toxicity

Grade (n)*

Grade 3 or 4 (%)

1

2

3

4

Neutropenia

0

4

3

29

74.4

Leukopenia

5

8

19

4

54.8

Anemia

18

17

4

0

9.1

Thrombocytopenia

4

0

0

0

0

Nausea

13

15

8

0

22.2

Neurosensory effects

13

7

6

0

12.8

Vomiting

13

9

4

1

10.6

Neuromotor effects

9

9

5

0

10.6

Diarrhea

14

7

3

1

8.5

Allergic reactions

0

0

3

0

6.5

Infection

2

0

3

0

6.5

Neuro-mood

1

4

2

0

4.3

Mucositis

11

5

1

0

2.1

Hypotension

2

2

1

0

2.1

Alopecia

7

26

0

0

0

Fever in the absence of infection

5

9

0

0

0

Skin

10

4

0

0

0

Neuro-constipation

5

3

0

0

0

Pulmonary

1

3

0

0

0

Neuro-hearing

0

3

0

0

0

Hematologic†

Nonhematologic††

* The number of patients having one or more adverse events is given; the worst grade per patient is recorded. † Patients were evaluable if they had at least one blood count between day 6 and day 15. n=43 for neutropenia and thrombocytopenia, n=44 for anemia, and n=42 for leukopenia. †† Patients with ≥ 5% acute nonhematologic NCI-gradable toxicity, possibly or probably related to study medication. n=47, except for infection where n=46 because information was missing for one patient. .ECKHA 

Cumulative Probability

evaluable for response. The overall response rate for evaluable patients was 37.5% (95% CI; 22.5, 52.5). One patient (2.5%) achieved a complete response, 14 (35.0%) had partial responses, 17 (42.5%) had stable disease, and 8 (20.0%) had disease progression. Of the 7 patients who were not evaluable for response, 5 had no follow-up tumor assessments after receiving either 1 or 2 treatment cycles and 2 patients were not evaluable because they discontinued study treatment due to anaphylactic reactions before completing cycle 1. The time to response for the complete responder was 5 weeks and the duration of the complete response was 32 weeks. The time to response for the partial responders ranged from 3 to 20 weeks and the duration of the partial responses ranged from 11 to 48 weeks. The median duration of response was 34.6 weeks (range, 11 - 48+ weeks) and the median time to disease progression was 18.9 weeks (range, 0 to 67 weeks). Figure 1 shows the overall survival of all patients. The median survival was 11.3 months. Ten patients were still alive at the data cutoff point of April 30, 1999. Survival times ranged from 2.4 to 49.8+ months.

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0

0 2 4 6 8 10 12 14 16 18 20 22 24 Survival (months)

Kaplan-Meier survival curve for patients with advanced non–small-cell lung cancer treated with docetaxel (75 mg/m2) and cisplatin (75 mg/m2).

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Docetaxel/Cisplatin in Patients with Lung Cancer Table 4

Modified Functional Assessment of Cancer Therapy-Lung (FACT-L) Scores Before and During Treatment with Docetaxel/Cisplatin Combination Therapy Patients

Mean (SD) Score at Baseline

Mean (SD) Score During Treatment*

Mean (SD) Change From Baseline 

P-value  

TOI-PFL

32

57.0 (12.5)

56.3 (9.5)

-0.7 (11.6)

0.745

TOI-PFT

32

86.1 (12.1)

78.1 (13.0)

-8.0 (12.5)

0.001

Total

32

143.6 (17.6)

138.6 (16.8)

-5.1 (15.8)

0.079

SFWB

32

23.7 (3.2)

22.6 (3.5)

-1.1 (3.9)

0.120

EWB

32

14.1 (4.3)

15.9 (3.6)

1.8 (2.3)

<0.001

FACT-L Subscale

Primary Endpoint

Secondary Endpoint

* Treatment scores were determined for 32 patients with at least one treatment FACT-L assessment (after cycle 3, cycle 5, or week 26) plus a baseline assessment. † Mean treatment score minus baseline score. †† Paired t-test. TOI-PFL (21 items), Physical well-being + Functional well-being + Lung cancer subscale; TOI-PFT (27 items), Physical well-being + Functional wellbeing + Taxane toxicity subscale; Total (46 items), Total quality of life score (Physical well-being + Social/Family well-being + Emotional well-being + Functional well-being + Lung cancer subscale + Taxane toxicity subscale); SFWB (7 items), Social/Family well-being; EWB (5 items), Emotional well-being; SD, standard deviation.

Grade 3 or 4 neutropenia was observed in 74.4% of patients (Table 3) and 55.4% of cycles. The median neutrophil nadir was 0.3 x 10 3 mm 3 (range, 0 to 4.2 x 10 3 mm 3) and the median time to neutropenia nadir was 9 days (range, 6 to 14 days). The median time to recovery from grade 3 or 4 nadir to grade 0 was 7 days (range, 1 to 17 days). Febrile neutropenia was observed in 12.8% of patients and 4.5% of cycles. Anemia and thrombocytopenia were infrequent.

SGOT were observed in 29.5% and 26.8% of patients, respectively. A total of 34 serious adverse events possibly or probably related to study medication were reported in 23 patients. The most frequently occurring serious adverse event was febrile neutropenia (12.8%). Three patients died of causes unrelated to the study drug while undergoing treatment. One died from a pulmonary hemorrhage caused by malignant disease, one due to infection, and one from cardiopulmonary arrest due to a preexisting aneurysm.

Nonhematologic Toxicity

Quality of Life

All treated patients experienced at least one NCI-gradable adverse event that was possibly or probably related to study medication. In most cases, these events were classified as grade 1 or 2 (Table 3). Grade 3 or 4 toxicities included: nausea (eight patients), neurosensory effects (six), neuromotor effects (five), vomiting (five), diarrhea (four), infection (three), allergic reactions (three), mood disturbances (two), mucositis (one), and hypotension (one). Most occurrences of non-NCI-gradable adverse events possibly or probably related to treatment were of mild to moderate intensity. Fluid retention was observed in 53.2% of patients, but in no case was it severe. The median cumulative dose-to-fluid retention was 226 mg/m2. Severe asthenia was seen in 14.9% of patients. Other toxicities observed in > 10% of patients were anorexia (40.4%), mucous membrane disorder (36.2%), dehydration (17.0%), nail disorder (14.9%), taste perversion (14.9%), insomnia (12.8%), dry mouth (10.6%), arthralgia (10.6%), and abdominal pain (10.6%). Most biochemical toxicities were classified as grade 1 or 2. The most frequently occurring biochemical toxicities were hypomagnesemia (50.0%), elevated alkaline phosphatase (48.8%), and hypocalcemia (47.6%). Elevated creatinine and

All but one patient completed the modified FACT-L at baseline (within 7 days prior to starting treatment). Thirtythree patients completed 3 cycles of treatment; 25 of those 33 patients (69.7%) completed the FACT-L test. Nine tests were completed on day 1 of cycle 3, 14 were completed within 2 days prior to starting cycle 3, two were completed 3 to 7 days prior to the start of cycle 3, and eight were not completed at all. At cycle 5, the majority of patients (60.7%) completed the test. At least 50% of patients received 5 or more cycles of treatment. Only 3 assessments were completed for the week 26 time-point. Twenty-three FACT-L assessments were obtained at various other times during treatment. Thirty-two patients were considered evaluable for quality of life analysis because these patients had a baseline analysis in addition to one other quality of life assessment during the study (Table 4). The average TOI-PFL (Trial Outcome IndexPhysical/Functional Well-Being) score during treatment was 56.3, a statistically insignificant difference from the baseline score of 57.0. A statistically significant (P = 0.001) decrease in the mean TOI-PFT (Trial Outcome Index-Physical/Functional Well-being and Taxane Toxicity) score was observed (Table 4). These findings indicate that patients did not seem

Safety Profile Hematologic Toxicity

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Chandra P. Belani et al Table 5

Docetaxel Combined with Cisplatin in NSCLC: Comparison of Phase II Studies Present Study

Zalcberg et al17

Le Chevalier et al22

Georgoulias et al23

47

47

51

53

Docetaxel

75 mg/m2

75 mg/m2

75 mg/m2

100 mg/m2

Cisplatin

75 mg/m2

75 mg/m2

100 mg/m2

80 mg/m2

Filgrastim

-

-

-

+

Number of patients enrolled Schema

Efficacy 40

36

42

53

37.5%

38.9%

33.3%

45.2%

Time to progression*

4.7 months

4.1 months

3.7 months

7.8 months

Median survival*

11.3 months

9.6 months

8.4 months

13.4 months

12.8%

13%

15%

28%

Nausea (grade 3 or 4)

17%

25%

14%

6%

Diarrhea (grade 3 or 4)

8%

13%

6%

11%

Neurosensory (grade 3)

12%

2%

2%

9%

Evaluable patients Overall response rate

Salient Toxicities (% of patients) Febrile neutropenia

*Time to progression and median survival are calculated for the intent-to-treat population.

to experience a change in lung cancer–specific symptoms/ concerns, but did report worsening neurotoxicity. The following three secondary quality of life endpoints were also evaluated: total FACT-L score, SFWB (social/family well-being), and EWB (emotional well-being). There was a slight decrease in the total FACT-L score, from 143.6 at baseline to 138.6 during treatment, but this was not statistically significant. Patients reported no change in SFWB, but did report a statistically significant increase in EWB (P < 0.001) from a mean score of 14.1 at baseline to 15.9 during treatment. Quality of life scores were compared between tumor response groups. Quality of life scores were available for 15 patients who had achieved an objective response, 8 patients with stable disease, and 9 patients with disease progression. No differences in FACT-L scores were found between tumor response groups; mean baseline quality of life scores, as well as the mean change scores, were similar among the 3 groups.

Discussion This study confirmed the feasibility and efficacy of docetaxel and cisplatin in patients with advanced and metastatic NSCLC. The response rate of 31.9% and median survival of 11.3 months observed in the intent-to-treat population were comparable to those observed by Zalcberg et al17 (29.8% and 9.6 months) and by Le Chevalier et al 22 (27.4% and 8.4 months). The response rates in evaluable patients in each study were higher as shown in Table 5. In addition, the toxicity profile was comparable to the present study. The highest response rate (45.2%) and longest median survival (13.4 months) were observed in the study conducted by Georgoulias and colleagues, 23 in which docetaxel was administered at 100 mg/m2 (Table 5). However, increasing

the dose of docetaxel to 100 mg/m2 was also associated with an increase in myelosuppression, despite the use of granulocyte colony-stimulating factor (G–CSF) as primary prophylaxis; febrile neutropenia was observed in 28% of patients, as opposed to 12.8% in the present study. Whether the addition of cisplatin to docetaxel increases the overall efficacy in patients with NSCLC is not well established; it appears, however, that the doublet produces higher response rates. Conversely, it has been clearly recognized that the addition of one of the novel agents such as gemcitabine, vinorelbine, or tirapazamine to cisplatin improves both response rates and survival of patients with advanced NSCLC compared to cisplatin alone.6-7,24 Cisplatin- or carboplatin-based doublets continue to be the "standard of care" for patients with NSCLC. A recent comparison of a noncisplatin regimen, docetaxel and gemcitabine, with the combination of docetaxel and cisplatin suggested that the platinum compounds still cannot be eliminated from the regimens used in the management of patients with advanced NSCLC.25 In the future, the search for the "optimal," "definitive," and "ideal" chemotherapeutic regimen for advanced NSCLC will be based not only on efficacy parameters, but also on improved quality of life. In this study, quality of life was assessed using the FACT-L instrument which has been shown to be a reliable and valid method for measuring quality of life in patients with lung cancer.21,26 No change was observed in the mean TOI-PFL score, which indicates that patients did not experience a change in lung cancer-specific symptoms/ concerns following treatment, although patients did report worsening neurotoxicity following treatment (indicated by a decrease in the mean TOI-PFT score). Analysis of secondary quality of life endpoints indicated that there was a slight

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Docetaxel/Cisplatin in Patients with Lung Cancer improvement in total quality of life scores following treatment, although this was not statistically significant. Furthermore, despite no effect on social and family well-being, a statistically significant improvement in emotional well-being was reported following docetaxel/cisplatin treatment. To detect meaningful differences in quality of life, it is necessary to conduct large-scale randomized trials. Based on the activity observed in this trial, the combination of docetaxel 75 mg/m2 and cisplatin 75 mg/m2 (given as 1-hour infusions every 3 weeks) is being evaluated in a large, randomized ECOG study for patients with advanced and metastatic NSCLC.

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