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Keywords:

  • nonsmall cell lung cancer;
  • docetaxel;
  • gemcitabine;
  • elderly patients;
  • stage IV NSCLC;
  • poor performance status patients

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

BACKGROUND.

The aim of this study was to compare the efficacy of single-agent weekly docetaxel with the combination of docetaxel and gemcitabine in elderly and/or poor performance status patients with advanced nonsmall cell lung cancer (NSCLC).

METHODS.

Previously untreated patients with stage IIIB/IV NSCLC who were either >65 years old or had an Eastern Cooperative Oncology Group (ECOG) performance status 2 were eligible. Patients were randomized to receive weekly docetaxel (36 mg/m2) Days 1, 8, and 15 or docetaxel (30 mg/m2)/gemcitabine (800 mg/m2) Days 1, 8, and 15. Both regimens were repeated on 28-day cycles for 6 cycles or until disease progression.

RESULTS.

Three hundred fifty patients were randomized, and 345 received treatment. The median age of patients was 74 years; 38% were >75 years old, and 35% had ECOG performance status 2. Intent-to-treat analysis showed median survivals of 5.5 months versus 5.1 months in the groups receiving docetaxel/gemcitabine versus weekly docetaxel, respectively (P = .65). There were no survival differences detected with docetaxel/gemcitabine versus weekly docetaxel in the 223 patients with good performance status (7.2 months vs 8.0 months, respectively) or in the 122 poor performance status patients (3.8 months vs 2.9 months, respectively). Median time-to-progression was longer in patients who received docetaxel/gemcitabine (4.8 months vs 2.9 months; P = .004). Both regimens were generally well tolerated.

CONCLUSIONS.

Treatment with docetaxel/gemcitabine produced a modest improvement in time-to-progression but had no impact on survival when compared with single-agent weekly docetaxel in this group of patients. Results with both regimens were disappointing, particularly in patients with poor performance status. Improved treatment for these patients will require the introduction of novel, well-tolerated, targeted agents. Cancer 2007. © 2007 American Cancer Society.

Treatment with platinum-based combination chemotherapy improves survival in patients with advanced nonsmall cell lung cancer (NSCLC) who have good performance status, and platinum-based combination chemotherapy is now considered the standard of care.1–4 However, the optimal treatment of patients who are elderly or who have poor performance status is less clearly defined. Platinum-based regimens have consistently produced more toxicity in these patient groups when compared with treatment of younger patients.5–7 Efficacy evaluations of various regimens have produced somewhat more conflicting results. In retrospective subset analyses of large phase 3 trials, elderly patients with good performance status and younger patients derived similar benefit from treatment with platinum-based combinations.2, 5, 6 However, in a large phase 3 trial designed specifically for elderly patients, single-agent treatment with either gemcitabine or vinorelbine was equivalent to the nonplatinum-containing combination of gemcitabine/vinorelbine.8

To further investigate the optimal treatment for elderly and poor performance status patients, we performed a randomized phase 3 study that compared single-agent versus combination chemotherapy. For the single agent, we chose weekly docetaxel, which we had previously demonstrated to be active and well tolerated in this patient population.9 At the time we started this trial, there was less information on weekly docetaxel than either gemcitabine or vinorelbine. However, single-agent docetaxel has since been found to be more active than vinorelbine.10 For the combination regimen, we chose docetaxel/gemcitabine, a regimen we had previously evaluated in a phase 2 trial.11 When we compared our sequential phase 2 trials, the overall response rates (28% vs 19%) and median survivals (7 months vs 5 months) suggested an improvement with docetaxel/gemcitabine versus single-agent docetaxel. However, these relatively small differences led us to a more definitive comparison; results of our randomized phase 3 trial are now reported.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Patient enrollment in this multicenter, randomized, phase 3 study was initiated in August 2001. This study was conducted within the Minnie Pearl Cancer Research Network, a community-based, collaborative, clinical trials group.

Patient Eligibility

Patients eligible for this study were required to have American Joint Commission on Cancer stage IIIB or stage IV, biopsy-proven NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, or mixtures of these histologies). Patients with stage IIIB disease were eligible only if they had malignant pleural effusions. In addition, patients were required to be older than 65 years of age or to be poor candidates for standard platinum-based chemotherapy regimens because of either coexistent medical illness or poor performance status. Patients were required to be previously untreated with chemotherapy; previous surgical resection and/or radiation therapy was permitted. Additional inclusion criteria included Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2; measurable or evaluable disease; adequate bone marrow function (absolute neutrophil count [ANC] ≥1500/μL, platelets ≥100,000/μL, hemoglobin ≥8 g/dL); adequate liver function (serum bilirubin <1.4 mg/dL, and serum glutamic oxaloacetic transaminase [SGOT] <2.5× upper limits of normal); serum creatinine ≤2.0 mg/dL.

Patients were excluded if they had parenchymal brain metastases or meningeal metastases. The single exception was the patient with a solitary brain metastasis, previously treated with definitive resection and/or radiation therapy, with no residual metastasis on computed tomography (CT) scanning or magnetic resonance imaging (MRI). Other excluded patients included those who had had a major surgical procedure within 4 weeks; pre-existing peripheral neuropathy >grade 1; other invasive cancers treated within 5 years; and pregnant or lactating females.

All patients were required to give written informed consent before study entry. This study was approved by the TriStar Institutional Review Board and by the local institutional review boards of all participating network sites.

Pretreatment Evaluation

Before beginning therapy, all patients were evaluated with routine history, physical examination, chemistry profile, and complete blood counts. Tumor staging included CT scans of the chest and abdomen. In addition, either CT or MRI of the head was required. A radionuclide bone scan or a positron emission tomographic (PET) scan was also required in patients with skeletal symptoms. All radiologic evaluation was performed within 3 weeks of study entry; laboratory evaluations were performed within 1 week of study entry.

Treatment Plan

Patients were randomized to receive either weekly docetaxel as a single agent (Regimen A) or the combination of docetaxel + gemcitabine (Regimen B). Patients randomized to Regimen A received docetaxel 36 mg/m2 by 30-minute intravenous infusion on Days 1, 8, and 15 of a 28-day cycle. Patients randomized to Regimen B received gemcitabine 800 mg/m2, 30-minute IV infusion, followed by docetaxel 30 mg/m2, 30-minute IV infusion; both drugs were administered on Days 1, 8, and 15 of a 28-day cycle. Standard hypersensitivity and antiemetic prophylaxis were administered before each dose of chemotherapy.

All patients were re-evaluated for response to treatment after they had completed 2 courses (8 weeks) of therapy. Patients with objective response or stable disease at the time of re-evaluation continued therapy, and they were reevaluated every 8 weeks. Patients continued treatment until disease progression or for a recommended 6 courses (24 weeks) of therapy.

Dose Modifications

Parameters for dose modifications necessitated by myelosuppression were based on blood counts on the day of scheduled treatment and were identical for Regimens A and B. Patients with ANC >1500/μL and platelet count >100,000/μL received a full dose of treatment. Patients with an ANC of 1000–1500/μL or a platelet count of 75,000–100,000/μL received a 75% dose. Patients with ANC <1000/μL or platelet count <75,000/μL had the scheduled dose omitted, and they were re-evaluated on the day of the next scheduled treatment. If the counts had improved to ANC >1000/μL and platelet count >75,000/μL, then patients received treatment with 75% doses. The duration of each course of treatment was always 28 days. If patients had a dose omitted because of myelosuppression, the treatment cycle was not lengthened; rather, the patient was re-evaluated on the date of the next scheduled dose, and treatment proceeded as described above. A maximum of 2 dose reductions were allowed; if myelosuppression continued to limit dosing, then the patient was removed from study. If blood counts failed to return to acceptable minimum levels after 3 weeks, the patient was removed from study. Growth factors (G-CSF or GM-CSF) were not used routinely in this study, and they were not substituted for a protocol-mandated dose modification. However, use of growth factors during treatment of neutropenic fever, or as prophylaxis following such an episode, was at the discretion of the treating physician.

Patients who experienced other grade 3 or 4 nonhematologic toxicities (with the exception of nausea, vomiting, or alopecia) had treatment withheld until the toxicity had improved to grade 1 or less. Treatment was then resumed using a 75% dose of the offending drug. Any grade 3 or 4 nonhematologic toxicity that did not improve to ≤grade 1 after 3 weeks resulted in the discontinuation of treatment.

Definition of Treatment Response

All patients who received 8 weeks of therapy were assigned a response category by their treating physician based on World Health Organization (WHO) criteria.12 (At the time this study was designed in late 2000, the Response Evaluation Criteria In Solid Tumors [RECIST] criteria had not yet become the standard method of evaluating response to treatment.) In this study, there was no central review for confirmation of responses.

Statistical Analysis

The primary objective of this study was to determine whether the addition of gemcitabine to docetaxel improved survival when compared with treatment results with single-agent weekly docetaxel. The secondary objectives were to compare the objective response rates, time to tumor progression, and toxicities of these 2 regimens. On the basis of previous clinical trials, treatment with weekly docetaxel was expected to result in a 1-year survival rate of approximately 25% in this group of patients. To detect an improvement of the 1-year survival to 40% with docetaxel/gemcitabine, randomization of a total of 330 patients was required (statistical type 1 error of 5% and type 2 error of 20%). Assuming that approximately 5% of elderly patients entering trials for advanced NSCLC are not evaluable for various reasons, the accrual goal for this trial was 346 patients.

Overall survival and time-to-progression were plotted by Kaplan-Meier estimates,13 and differences between groups were calculated according to the log-rank test. Differences between groups for response rate, baseline characteristics, and toxicity were analyzed with the chi-square test. Time-to-progression was measured from the date of first treatment until the date of documented tumor progression. Overall survival was measured from the date of first treatment until the date of death. All patients who received at least 1 dose of treatment were included in the toxicity comparisons. Toxicity was measured by Common Toxicity Criteria, Version 2.0 (published by the National Cancer Institute, Cancer Therapy Evaluation Program).

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Patient Characteristics

Between August 2001 and March 2006, 350 patients were enrolled by 39 participating sites in the Minnie Pearl Cancer Research Network (Table 1). Five patients never received any treatment and are included only in the intent-to-treat analyses. Characteristics of the 345 patients who received at least 1 dose of treatment are summarized and compared in Table 2. One hundred seventy-one patients received weekly docetaxel, and 174 received docetaxel/gemcitabine. The median age for all patients in this study was 74 years (range, 45 years to 91 years). Clinical characteristics of these 2 groups were comparable, including age, sex, performance status, histology, and stage. Overall, 35% of patients in this trial had poor performance status (ECOG-PS 2), and 132 (38%) patients were older than 75 years. A total of 34 (10%) patients were younger than 65 years; all of these patients had poor performance status (ECOG-PS 2).

Table 1. Minnie Pearl Cancer Research Network Participating Sites
SiteLocation
Tennessee Oncology, PLLCNashville, Tenn
Wellstar Health System Cancer ResearchMarietta, Ga
Consultants in Blood Disorder and CancerLouisville, Ky
Graves-Gilbert ClinicBowling Green, Ky
Oncology Associates of Western KentuckyPaducah, Ky
Mary Bird Perkins Cancer CenterBaton Rouge, La
Louisiana Oncology AssociatesLafayette, La
The Medical Oncology Group, PAGulfport, Miss
Spartanburg Regional Medical CenterSpartanburg, SC
McLeod Cancer and Blood CenterJohnson City, Tenn
Greenview Regional HospitalBowling Green, Ky
Terrebonne General Medical CenterHouma, La
Northeast Georgia Medical CenterGainesville, Ga
Jackson Oncology AssociatesJackson, Miss
Northeast Alabama Regional Medical CenterAnniston, Ala
Phoebe Cancer CenterAlbany, Ga
Oncology and Hematology AssociatesRoanoke, Va
Medical Oncology, LLCBaton Rouge, La
Associates in Hematology and OncologyChattanooga, Tenn
Thompson Cancer Survival CenterKnoxville, Tenn
Northeast Arkansas ClinicJonesboro, Ark
Oncology Hematology Associates of Southwest IndianaEvansville, Ind
South Texas Oncology & HematologySan Antonio, Tex
Baton Rouge General Medical Center–Cancer ResearchBaton Rouge, La
Methodist Cancer Center–Oncology Research DepartmentOmaha, Neb
Central Georgia Cancer Care, PCMacon, Ga
Kingsport Hematology–Oncology AssociatesKingsport, Tenn
Columbia OncologyColumbia, Tenn
Cancer Research Aultman HospitalCanton, Ohio
Florida Cancer SpecialistsFort Myers, Fla
Montana Cancer Institute FoundationMissoula, Mont
Watson Clinic Center for ResearchLakeland, Fla
Cancer Care ServicesPortsmouth, NH
Atlantic Hematology Oncology AssociatesManasquan, NJ
Oncology Hematology Care, IncCincinnati, Ohio
Mercy HospitalPortland, Me
Online Collaborative Oncology GroupMemphis, Tenn
Table 2. Patient Characteristics
CharacteristicNo. of patients (%)
Docetaxel n = 171Docetaxel/Gemcitabine n = 174
  1. ECOG indicates Eastern Cooperative Oncology Group.

Patient age, y, median [range]74 [45–90]74 [47–91]
 <6518 (11)16 (9)
 65–7038 (22)41 (24)
 71–7548 (28)52 (30)
 >7567 (39)65 (37)
Sex
 Men105 (61)108 (62)
 Women66 (39)66 (38)
ECOG performance status
 015 (9)11 (6)
 199 (58)98 (56)
 257 (33)65 (37)
Histology
 Adenocarcinoma65 (38)67 (38)
 Squamous carcinoma38 (22)29 (17)
 Large cell carcinoma37 (22)41 (24)
 Mixed histologies1 (1)3 (2)
 Nonsmall cell carcinoma (not otherwise specified)30 (17)34 (19)
Stage
 IIIB46 (27)41 (24)
 IV125 (73)133 (76)
Site of treatment
 Sarah Cannon Research Institute76 (44)71 (41)
 Network sites95 (56)103 (59)

Treatment Administration

The 345 patients who were treated in this clinical trial received a total of 1017 treatment cycles (docetaxel, 483 cycles; docetaxel/gemcitabine, 534 cycles). The median number of cycles per patient was 2 for both treatments used in this trial. Only 11% and 14% of patients receiving docetaxel and docetaxel/gemcitabine, respectively, completed the planned 6 cycles of treatment. The main reason for discontinuation of treatment was disease progression (weekly docetaxel, 64%; docetaxel/gemcitabine, 55%). Treatment was stopped prematurely because of treatment-related toxicity in 15 (9%) patients who were receiving weekly docetaxel, and in 22 (13%) patients who were receiving docetaxel/gemcitabine. The remaining patients (weekly docetaxel, 29 patients; docetaxel/gemcitabine, 31 patients) were removed from treatment for a variety of reasons (eg, patient request, intercurrent illness, physician decision); however, it is likely that most of these patients also had progressive NSCLC that caused their decline in performance status.

During the first 2 courses of therapy, the percentage of planned treatment administered in each arm was as follows: weekly docetaxel, 95%; docetaxel/gemcitabine, 84%.

Intent-to-Treat Analysis

At the time of analysis, 32 patients were alive after a median follow-up of 22 months (range, 9 months to 52 months). Figure 1 shows a comparison of the overall survival of patients treated with weekly docetaxel versus docetaxel/gemcitabine, based on an intent-to-treat analysis of all 350 randomly assigned patients. Survival comparisons for the weekly docetaxel and docetaxel/gemcitabine study arms, respectively, showed no significant differences (P = .65) and were as follows: median survival, 5.1 months versus 5.5 months; 1-year survival rate, 24% versus 26%; and 2-year survival rate, 9% versus 8%.

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Figure 1. Overall survival in relation to treatment, intent-to-treat analysis (n = 350). The median survivals for docetaxel/gemcitabine and weekly docetaxel were 5.5 vs 5.1 months, respectively.

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Analyses According to Protocol

After excluding, according to protocol, the 5 patients who did not receive any treatment, 345 patients (weekly docetaxel, n = 171; docetaxel/gemcitabine, n = 174) remained by protocol for analyses. Comparison of the treated groups is almost identical to the intent-to-treat population and shows no survival difference based on treatment received (docetaxel/gemcitabine, 5.6 months; docetaxel, 5.1 months; P = .64).

Because elderly patients with good performance status are now recognized as a distinct group from patients with poor performance status, these 2 subsets are compared separately. Figure 2 compares the overall survival of all good performance status patients in this trial treated with weekly docetaxel (n = 114) versus docetaxel/gemcitabine (n = 109). Although both subgroups had modestly better outcomes (median survivals, 8.0 months vs 7.2 months, respectively), survival was not statistically different (P = .5) when these subgroups were compared. Separate comparisons of good performance status patients >70 years and >75 years of age also showed no differences on the basis of treatment regimen. Both treatments performed poorly in patients with ECOG performance status 2; patients who received docetaxel (n = 57) had a median survival of 2.9 months versus 3.8 months (P = .62) for patients who received docetaxel/gemcitabine (n = 65) (Fig. 3).

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Figure 2. Overall survival comparisons in good performance status patients (ECOG 0 or 1). Median survivals were docetaxel/gemcitabine, 7.2 months; weekly docetaxel, 8.0 months.

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thumbnail image

Figure 3. Overall survival comparisons in poor performance status patients (ECOG-PS 2). Median survivals were docetaxel/gemcitabine, 3.8 months; weekly docetaxel, 2.9 months.

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Time-to-Progression

Among the 345 patients considered eligible for analysis according to protocol, the median time-to-progression was 2.9 months (95% confidence interval [CI], 2.0–3.6 months) for patients who received weekly docetaxel versus 4.8 months (95% CI, 3.9–6.2 months) for those who received docetaxel/gemcitabine (P = .004) (Fig. 4). The percentage of progression-free patients at 1 year was also higher for patients who received docetaxel/gemcitabine (11% vs 21%).

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Figure 4. Time-to-progression (TTP) in patients treated in accord with protocol (n = 345). Docetaxel/gemcitabine treatment produced longer total TTP than did weekly docetaxel (4.8 months vs 2.9 months, respectively; P = . 004).

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Overall Response Rate

A total of 256 patients received at least 2 courses of treatment and were evaluable for response (weekly docetaxel, n = 130; docetaxel/gemcitabine, n = 126). Of the 130 evaluable patients who received weekly docetaxel, there were 2 complete responders and 20 partial responders (overall response rate 17%; 95% CI, 11%–24%). Of the 126 patients who were evaluated after 2 courses of docetaxel/gemcitabine, 32 patients had partial responses (overall response rate 25%; 95% CI, 18%–34%; P = .10).

Toxicity

A total of 345 patients (weekly docetaxel, n = 171; docetaxel/gemcitabine, n = 174) received at least 1 dose of study drug and were included in the toxicity analysis. The grade 3 and 4 toxicities encountered by patients treated in this trial are summarized in Table 3. Both treatments were well tolerated by most patients. The incidence of grade 3 or 4 neutropenia, thrombocytopenia, and anemia was significantly higher in patients who received docetaxel/gemcitabine. In addition, more patients who were receiving docetaxel/gemcitabine required erythrocyte transfusions. Hospitalization for treatment of neutropenic fever was uncommon with either treatment. Severe nonhematologic toxicity was uncommon; fatigue was the only adverse event that occurred in >10% of patients. One patient who was receiving docetaxel/gemcitabine developed fatal pulmonary infiltrates with hypoxia, possibly related to treatment.

Table 3. Grade 3 and 4 Toxicity
ToxicityNo. of patients (%)
Docetaxel n = 171Docetaxel/gemcitabine n = 174P
Grade 3 Grade 4Grade 3 Grade 4
Hematologic
 Neutropenia8 (5) 5 (3)19 (11) 14 (8).002
 Thrombocytopenia3 (2) 5 (3)21 (12) 6 (3).001
 Anemia2 (1) 7 (4)18 (10) 6 (3).007
 Neutropenia/fever1 (1)3 (2) 
 Bleeding episodes3 (2)5 (3) 
 RBC transfusions3 (2)22 (13)<.001
Nonhematologic
 Fatigue27 (16) 2 (1)35 (20) 2 (1) 
 Nausea/vomiting16 (9) 06 (3) 0 
 Diarrhea8 (5) 011 (6) 0 
 Arthralgia/myalgia3 (2) 09 (5) 0 
 Constipation1 (1) 06 (3) 1 (1) 
 Edema1 (1) 1 (1)3 (2) 2 (1) 
 Hyperglycemia4 (2) 02 (1) 0 
 Peripheral neuropathy1 (1) 03 (2) 1 (1) 
 Hypersensitivity reaction2 (1) 1 (1)1 (1) 0 
 Stomatitis0 03 (2) 0 
 Rash1 (1) 02 (1) 0 
 Hyperlacrimation2 (1) 00 0 
 Nail toxicity1 (1) 01 (1) 0 

Both treatment regimens were tolerable in all patient subgroups, including patients with poor performance status and those aged 75 years or older. A higher percentage of poor performance status reported treatment-related fatigue with either regimen (docetaxel, 21% vs 15%; docetaxel/gemcitabine, 22% vs 16%). The rates of hematologic toxicity and other nonhematologic toxicities did not vary significantly with age or performance status.

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The treatment of advanced NSCLC remains difficult, particularly in patients who are elderly or have poor performance status. When this trial was designed, limited data were available on the efficacy of new nonsmall cell lung cancer regimens in these patients, and it was common to consider elderly and poor performance status patients as a single, large group. The currently accepted definition of “elderly” as being >70 years of age was also less firmly established. More recently, it has become increasingly evident that this population is heterogeneous; patients with poor performance status consistently have short median survival, whereas some elderly patients with good performance status have prognoses similar to that of younger patients. This favorable subset of elderly patients (ie, good performance status, usually <75 years of age) has recently been highlighted in retrospective subset analyses of several large randomized trials.2, 5, 6, 14, 15 In these trials, patients older than 70 years derived similar benefits from 2-drug, platinum-based regimens as did the entire group. In the Cancer and Leukemia Group B (CALGB) trial reported by Lilenbaum, patients who were ages 70 years and older (27% of the study population) had superior outcomes when treated with the combination of carboplatin/paclitaxel versus paclitaxel alone, similar to results found in the entire study population.2 Although not yet confirmed by prospective trial results, current recommendations for treatment of elderly patients with good performance status are identical to those for younger patients with good performance status.

Despite convincing data in selected good performance status elderly patients, it remains difficult to estimate the frequency of these patients among the entire group of elderly and/or poor performance status patients. In all of the phase 3 trials from which retrospective subset analyses arose, elderly patients accounted for <30% of the total patient population, and the large majority of these were between 70 and 75 years of age.2, 5, 14, 15 Limited evaluation is available on treatment outcomes of patients aged 75–80 years; those older than 80 years have consistently tolerated treatment poorly and had inferior outcomes.16, 17 It is clear that a sizeable percentage of elderly patients are not ideal candidates for platinum-based doublets, based on either poor performance status or greatly advanced age.

Considerable effort has been focused on the development of effective regimens for elderly patients that are better tolerated than the traditional platinum-based combinations. Several single agents have demonstrated activity in this patient population; vinorelbine proved superior to best supportive care in a randomized phase 3 trial.18 Recently, single-agent docetaxel produced superior survival when compared with single-agent vinorelbine in a randomized trial (14.3 months vs 9.9 months, respectively; P = .06).10 Nonplatinum-containing doublets, such as gemcitabine/vinorelbine, have also been well tolerated by elderly patients.8, 19 However, in 1 large randomized trial reported by Gridelli et al., the combination of gemcitabine/vinorelbine was no more effective than either agent used alone.8 Therefore, the benefit of nonplatinum doublets in this population has not been substantiated, and single-agent therapy remains the treatment of choice.

In the randomized phase 3 study reported here, we compared single-agent weekly docetaxel with the combination of docetaxel/gemcitabine. Both of the regimens were active and well tolerated by this patient group in our previously reported phase 2 trials.9, 11 Because we conducted this trial in a multicenter, community-based setting, the population of patients accrued is almost certainly different from those entered in large cooperative group trials. The median age of patients in this trial was 74 years, and 38% of patients were older than 75 years. In addition, 35% of patients had poor performance status (ECOG-PS 2). In this relatively heterogeneous group, the survival of patients who received single-agent docetaxel versus docetaxel/gemcitabine was similar. The time-to-progression was modestly improved with the combination regimen. Median survivals for both groups were disappointing (docetaxel, 5.1 months vs docetaxel/gemcitabine, 5.5 months), although similar to the 5-month median survival in our previous phase 2 trial of weekly docetaxel.9 When the subsets of patients with good performance status were compared, median survivals were substantially better (8.0 months vs 7.2 months, respectively), and they are similar to those reported in this patient population from large trials that used platinum-based doublets.2, 5, 14–16 Although the currently reported trial was not sufficiently large to allow a definitive comparison, docetaxel/gemcitabine and weekly docetaxel produced similar survival in this favorable subset of patients. As expected, median survivals for ECOG-PS 2 patients were poor in both groups (2.9 months vs 3.8 months, respectively).

The results of this randomized phase 3 trial, therefore, reinforce those previously reported by Gridelli et al. and provide further evidence that treatment with a single agent produces similar results and less toxicity than does a nonplatinum combination regimen. Although it may be appropriate to select patients with good performance status and <75 years of age for platinum-based combination regimens, single-agent treatment should be considered for the remainder of this large population. In the future, clinical trials should focus on more sharply defined subsets within this group. Specific subsets that require further evaluation are good performance status patients >75 years of age and patients with poor performance status.

Unfortunately, the results of this trial reveal the limitations of current therapy in this large group of lung cancer patients. It is likely that the modest benefit produced by 2-drug chemotherapy regimens in younger, good performance status patients is negated in an unselected group of elderly patients because of a combination of increased toxicity and difficulties in treatment delivery. In the future, substantial treatment advances in this group will require development of novel agents with better toxicity profiles.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
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    Langer CJ,Vangel M,Schiller J, et al. Age-specific subanalysis of ECOG 1594: fit elderly patients (70–80 yrs) with NSCLC do as well as younger patients (<70) [abstract]. Proc Am Soc Clin Oncol. 2003; 22: 639. (Abstract 2571).
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