Differences in attitudes and beliefs toward end-of-life care between hematologic and solid tumor oncology specialists.

BACKGROUND: Patients with hematologic malignancies often receive aggressive care at the end-of-life. To better understand the end-of-life decision-making process among oncology specialists, we compared the cancer treatment recommendations, and attitudes and beliefs toward palliative care between hematologic and solid tumor specialists. PATIENTS AND METHODS: We randomly surveyed 120 hematologic and 120 solid tumor oncology specialists at our institution. Respondents completed a survey examining various aspects of end-of-life care, including palliative systemic therapy using standardized case vignettes and palliative care proficiency. RESULTS: Of 240 clinicians, 182 (76%) clinicians responded. Compared with solid tumor specialists, hematologic specialists were more likely to favor prescribing systemic therapy with moderate toxicity and no survival benefit for patients with Eastern Cooperative Oncology Group (ECOG) performance status 4 and an expected survival of 1 month (median preference 4 versus 1, in which 1 = strong against treatment and 7 = strongly recommend treatment, P < 0.0001). This decision was highly polarized. Hematologic specialists felt less comfortable discussing death and dying (72% versus 88%, P = 0.007) and hospice referrals (81% versus 93%, P = 0.02), and were more likely to feel a sense of failure with disease progression (46% versus 31%, P = 0.04). On multivariate analysis, hematologic specialty [odds ratio (OR) 2.77, P = 0.002] and comfort level with prescribing treatment to ECOG 4 patients (OR 3.79, P = 0.02) were associated with the decision to treat in the last month of life. CONCLUSIONS: We found significant differences in attitudes and beliefs toward end-of-life care between hematologic and solid tumor specialists, and identified opportunities to standardize end-of-life care.

Optimisation of bronchial brachytherapy catheter placement with a modified airway stent.

Brachytherapy is a modality of treatment available for lung cancer with tracheal involvement. Correct positioning of the brachytherapy catheter is vital to the optimisation of treatment effect and reduction of complications. Normal airway anatomy and tumour location can make this positioning difficult. The current study presents the case of a 65-yr-old male with invasive tracheal squamous cell carcinoma of the anterior main carina involving the proximal left and right bronchus. The patient was successfully treated with brachytherapy using a novel modified airway stent with a traversing suture for positioning and stabilising the brachytherapy catheters and maximisation of the radiation effect. This simple yet innovative modification of readily available bronchoscopic equipment permits approximation and fixation of a brachytherapy catheter to any part of the proximal airway. Further analysis of this technique, including a prospective controlled trial, is planned.

The impact of induction chemotherapy on the outcome of second-line therapy with pemetrexed or docetaxel in patients with advanced non-small-cell lung cancer.

BACKGROUND: Using data from a large phase III study of previously treated advanced non-small-cell lung cancer (NSCLC) that showed similar efficacy for pemetrexed and docetaxel, this retrospective analysis evaluates the impact of first-line chemotherapy on the outcome of second-line chemotherapy. PATIENTS AND METHODS: In all, 571 patients with advanced NSCLC were randomly assigned to receive pemetrexed 500 mg/m(2) or docetaxel 75 mg/m(2) on day 1 of a 21-day cycle. Comparisons were made based on type of first-line therapy [gemcitabine + platinum (GP), taxane + platinum (TP), or other therapies (OT)], response to initial therapy, time since initial therapy, and clinical characteristics. The two second-line treatment groups were pooled for this analysis due to similar efficacy and were assumed to have no interaction with the first-line therapies. RESULTS: Baseline characteristics were generally balanced. By multivariate analysis, gender, stage at diagnosis, performance status (PS), and best response to first-line therapy significantly influenced overall survival (OS). Additional factors by univariate analysis, histology, and time elapsed from first- to second-line therapy significantly influenced OS. CONCLUSIONS: Future trials in the second-line setting should stratify patients by gender, stage at diagnosis, PS, and best response to first-line therapy.

Postoperative radiotherapy increases locoregional control of patients with stage IIIA non-small-cell lung cancer treated with induction chemotherapy followed by surgery.

PURPOSE: To determine the effectiveness of postoperative radiotherapy (RT) in patients with Stage IIB and Stage IIIA non-small-cell lung cancer (NSCLC) treated with induction chemotherapy followed by surgery. METHODS AND MATERIALS: We retrospectively reviewed the treatment records of 98 patients (58 men and 40 women; median age 61 years, range 31-91) with Stage IIB and Stage IIIA NSCLC who were treated with induction chemotherapy followed by surgery at our institution between January 1990 and December 2000. Patients were grouped by treatment (chemotherapy/surgery alone vs. chemotherapy/surgery/RT), by disease stage and nodal classification. The rates of local control (LC), disease-specific survival, disease-free survival, and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Of the 98 patients, 40 had Stage IIB and 58 had Stage IIIA. The clinical disease stage and N stage were significantly greater in those patients who underwent RT than in those who did not; however, no statistically significant differences were identified in the additional characteristics between those receiving and not receiving RT within each stage or nodal group. The overall 5-year actuarial LC rate was 81% in the RT group and 54% in the chemotherapy/surgery-alone group (p = 0.07). Postoperative RT significantly improved the 5-year LC rate in patients with Stage IIIA disease (from 35% to 82%, p = 0.01). Postoperative RT did not significantly improve the 5-year OS rate (30% with RT vs. 49% without) for all patients or for patients with Stage IIIA disease. The disease-specific survival and disease-free survival rates did not differ between the treatment groups. Patients who responded to induction chemotherapy had a significantly greater 5-year OS rate (49%) than did those with stable or progressive disease (22%, p = 0.003). CONCLUSION: Postoperative RT in patients with Stage IIIA NSCLC treated with induction chemotherapy followed by surgery significantly improved LC without improving OS. Significantly improved survival was observed in all patients who responded to induction chemotherapy compared with those with stable or progressive disease.

A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-small-cell lung cancer.

With the availability of chemotherapy agents for first- and second-line treatment of advanced non-small-cell lung cancer (NSCLC), the patient population that requires subsequent chemotherapy is increasing. This retrospective analysis was performed to describe the clinical course after two standard or approved chemotherapy agents in patients with good overall performance status. Data were selected from patients with advanced NSCLC who had received third- or fourth-line chemotherapy after two prior chemotherapy regimens that included platinum and docetaxel given concurrently or sequentially. Prior regiments had failed due to discase progression within 90 days of chemotherapy, or unacceptable toxicity. Examination of over 700 patient records between January 1993 and January 2000 at one US and one European cancer centre revealed 43 patients that fulfilled the inclusion criteria. Response rates decreased with each line of treatment: first line, 20.9%; second line, 16.3%; third line, 2.3%; and fourth line, 0%. The disease control rate (response plus stable disease) also decreased dramatically from first- to fourth-line treatment, although it was higher for second-line treatment (74.4%) than for first-line treatment (62.8%). The median overall survival time from diagnosis was 16.4 months. The median overall survival time from the start of the last treatment (either third or fourth line) was 4 months. Patients with stage III disease at diagnosis had a longer overall survival from diagnosis than patients with stage IV disease (P=0.02). This review highlights the need for novel therapy approaches for patients with recurrent NSCLC who have failed second-line therapy and provides a baseline for the statistical design of such studies.

Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: preliminary results.

A prospective randomized study was conducted to determine whether amifostine (Ethyol) reduces the rate of severe esophagitis and hematologic and pulmonary toxicity associated with chemoradiation or improves control of non-small cell lung cancer (NSCLC). Sixty patients with inoperable stage II or III NSCLC were treated with concurrent chemoradiotherapy. Both groups received thoracic radiation therapy (TRT) with 1.2 Gy/fraction, 2 fraction per day, 5 days per week for a total dose 69.6 Gy. All patients received oral etoposide (VP-16), 50 mg Bid, 30 minutes before TRT beginning day 1 for 10 days, repeated on day 29, and cisplatin 50 mg/m(2) intravenously on days 1, 8, 29, and 36. Patients in the study group received amifostine, 500 mg intravenously, twice weekly before chemoradiation (arm 1); patients in the control group received chemoradiation without amifostine (arm 2). Patient and tumor characteristics were distributed equally in both groups. Of the 60 patients enrolled, 53 were evaluable (27 in arm 1, 26 in arm 2) with a median follow-up of 6 months. Median survival times were 26 months for arm 1 and 15 months for arm 2, not statistically significantly different. Morphine intake to reduce severe esophagitis was significantly lower in arm 1 (2 of 27, 7.4%) than arm 2 (8 of 26, 31%; P =.03). Acute pneumonitis was significantly lower in arm 1 (1 of 27, 3.7%) than in arm 2 (6 of 26, 23%; P =.037). Hypotension (20 mm Hg decrease from baseline blood pressure) was significantly more frequent in arm 1 (19 of 27, 70%) than arm 2 (1 of 26, 3.8%; P =.0001). Only 1 patient discontinued treatment because of hypotension. These preliminary results showed that amifostine significantly reduced acute severe esophagitis and pneumonitis. Further observation is required to assess long-term efficacy.

Emerging therapies in non-small-cell lung cancer.

Lung cancer remains the single most devastating cause of cancer-related death with approximately 1.5 million cases of lung cancer expected worldwide and more than 1.3 million cancer-related deaths in 2001. In the United States alone, of 164,100 news cases expected in the year 2000, about 70,000 will be metastatic disease (stage IV), and another 70,000 will be locally advanced (stages IIIA and IIIB). Therefore, the five-year survival rate for lung cancer has improved only incrementally from 5% in the late 1950s to 14% by 1994. While advances in combined modality therapy have led to significant progress against locally advanced disease, it was only a decade ago that few believed that the treatment of stage IV non-small-cell lung cancer was justifiable. However, multiple randomized trials in the 1980s and 1990s have changed the role of chemotherapy in lung cancer, such that by the middle of the next decade, it may be that only patients with stage IA non-small-cell lung cancer are not considered as candidates for chemotherapy.

Docetaxel (Taxotere) shows survival and quality-of-life benefits in the second-line treatment of non-small cell lung cancer: a review of two phase III trials.

The potential benefits of docetaxel (Taxotere; Aventis, Antony, France) to patients with previously-treated non-small cell lung cancer have been evaluated in two prospective randomized phase III trials. In one study, patients with stage IIIB/IV non-small cell lung cancer who had failed previous cisplatin-based chemotherapy were randomized to receive either docetaxel (100 or 75 mg/m2, once every 3 weeks) or best supportive care. Median survival was significantly longer for patients treated with docetaxel 75 mg/m2 (7.5 months v 4.6 months) as was 1-year survival (37% v 11%). A second trial, also in platinum-pretreated patients, randomized patients to docetaxel 100 mg/m2, docetaxel 75 mg/m2, or vinorelbine/ifosfamide. Median survival was similar across the three study groups. Thirty-two percent of patients assigned to docetaxel 75 mg/m2 and 21% to docetaxel 100 mg/m2, were alive at 1 year, versus 19% on the vinorelbine/ifosfamide arm. Docetaxel offers clinically meaningful benefits in the second-line setting. The recommended dose is 75 mg/m2 once every 3 weeks. The adverse events observed were predictable, tolerable, and manageable. These phase III trials showed that docetaxel provided clinical benefits to patients with non-small cell lung cancer.

ZD1839 (Iressa) in non-small-cell lung cancer.

The epidermal growth factor receptor (EGFR) signaling pathway plays an important role in a number of processes that are key to tumor progression, including cell proliferation, angiogenesis, metastatic spread, and inhibition of apoptosis. EGFR is expressed or overexpressed in non-small-cell lung cancer (NSCLC), and EGFR-mediated growth has been associated with advanced disease and poor prognosis in NSCLC patients. ZD1839 (Iressa) is an orally active, selective EGFR-tyrosine kinase inhibitor that blocks EGFR signal transduction. In preclinical studies using NSCLC cell lines, ZD1839 has been shown to inhibit tumor cell growth. In addition, ZD1839, as monotherapy and in combination with commonly used cytotoxic agents, has produced growth delay in NSCLC human xenografts. Preliminary results from phase I trials in patients with advanced disease have shown that ZD1839 has excellent bioavailability, an acceptable tolerability profile, and promising clinical activity in patients with a variety of tumor types, particularly in NSCLC. ZD1839 is currently in phase III clinical development for the treatment of advanced NSCLC.

Second-line chemotherapy for non-small-cell lung cancer.

Most of the experience with second-line chemotherapy for non-small-cell lung cancer (NSCLC) comes from small phase II trials, which have shown disappointing or inconsistent results. The notable exception has been docetaxel, which has been extensively studied as a second-line therapy for NSCLC. On the basis of consistent phase II activity, two large randomized phase III trials were conducted for patients with advanced NSCLC that had progressed either on or after first-line platinum-based therapy. In one trial, docetaxel, at either 100 or 75 mg/m(2), was compared with a regimen of either vinorelbine or ifosfamide. In the second trial, docetaxel 75 to 100 mg/m(2) was compared with best supportive care. Both trials showed significant improvement in survival, time to progression, and quality of life in the patients receiving docetaxel versus the control therapy. Based on these two large trials, it appears that the use of second-line therapy with single-agent docetaxel at a dose of 75 mg/m(2) every 3 weeks is a reasonable practice in patients who maintain a good performance status.

Outcome predictors for 143 patients with superior sulcus tumors treated by multidisciplinary approach at the University of Texas M. D. Anderson Cancer Center.

PURPOSE: Superior sulcus tumors (SST) of the lung are uncommon and constitute approximately 3% of non-small cell lung cancer (NSCLC). These tumors cause specific symptoms and signs, and are associated with patterns of failure that differ from those seen for NSCLC tumors in other nonapical locations. Prognostic factors and most effective treatments are controversial. We conducted a retrospective study at The University of Texas M. D. Anderson Cancer Center to identify outcome predictors for patients with SST treated by a multidisciplinary approach. METHODS AND MATERIALS: This retrospective review of 143 patients without distant metastasis at presentation is a continuation of a previous M. D. Anderson study now updated to 1994. In this study, we examine the 5-year survival rate by pretreatment tumor and patient characteristics and by the treatments received. Strict criteria were used to define SST. Actuarial life-table analyses and Cox proportional hazard models were used to compare survival rates. RESULTS: Overall predictors of 5-year survival were weight loss (p < 0.01), supraclavicular fossa (p = 0. 03), or vertebral body (p = 0.05) involvement, stage of the disease (p < 0.01), and surgical treatment (p < 0.01). Five-year survival for patients with Stage IIB disease was 47% compared to 14% for Stage IIIA, and 16% for Stage IIIB. For patients with Stage IIB disease, surgical treatment (p < 0.01) and weight loss (p = 0.01) were significant independent predictors of 5-year survival. Among patients with Stage IIIA disease, the only predictor of survival was Karnofsky performance score (KPS) (p = 0.02). For patients with Stage IIIB disease, the only independent predictor of survival was a right superior sulcus location, which was associated with a worse 5-year survival rate than that for patients with tumors in the left superior sulcus (p = 0.02). More patients with adenocarcinoma than with squamous cell tumors experienced cerebral metastases within 5 years (p < 0.01). Patients without gross residual disease after surgical resection who received postoperative radiation therapy with total doses of 55 to 64 Gy had a 5-year survival rate of 82% as compared with the 5-year survival rate of 56% in patients who received 50 to 54 Gy. Twenty-three patients survived for longer than 3 years. Of these, 4 patients (17%) received radiation therapy alone or in combination with chemotherapy without surgical resection. The other 19 patients (83%) had resection combined with radiation therapy and/or chemotherapy. CONCLUSIONS: The findings from this study confirm the importance of the new staging system, separating T3 N0 M0 (Stage IIB) from Stage IIIA, since there was a significant difference in the 5-year survival (p < 0.01). Interestingly, there was no significant 5-year survival difference between Stage IIIA (N2) and Stage IIIB (T4 or N3). This study also suggests that surgery is an important component of the multidisciplinary approach to patients with SST if their nodes were negative. Disease that is minimally invading surrounding normal structures can be resected followed by radiation therapy in doses of 55 to 64 Gy. Further investigation of treatment strategies combining high-dose radiation therapy (>/=66 Gy) with chemotherapy is indicated for patients with unresectable and/or node-positive (N2) SST.

Phase II study of intravenous Doxil in malignant pleural mesothelioma.

Twenty-four patients with pleural mesothelioma received 50 mg/m2 of Doxil every four weeks. At follow-up, the disease had stabilized in 43% percent of patients and had progressed in 57%. No objective responses were observed. Estimated median survival of all patients was 37 weeks. Major toxicities were erythrodysesthesia of hands and feet and myelosuppression. No cardiac toxicity was observed. We concluded that Doxil at this dosage and schedule is inactive against pleural mesothelioma.

Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group.

PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m(2) (D100) or 75 mg/m(2) (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P =.001 and P =.036, respectively). Patients who received docetaxel had a longer time to progression (P =.046, by log-rank test) and a greater progression-free survival at 26 weeks (P =.005, by chi(2) test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P =.025, by chi(2) test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.

Adenocarcinoma of the lung in young patients: the M. D. Anderson experience.

BACKGROUND: Surveillance, Epidemiology, and End Results (SEER) data for the years 1973-1992 documented that patients age < 50 years presented with more advanced disease. Because of the increase in the incidence rate of lung adenocarcinoma in the past few decades and the presentation of more advanced disease in young patients, this study was performed to determine whether differences in survival exist between younger and older patients with this disease. METHODS: The authors reviewed the experience of the University of Texas M. D. Anderson Cancer Center between 1985-1994, encompassing 157 patients age < 40 years of 4097 patients registered with adenocarcinoma of the lung. For comparison, 157 patients age > 50 years with lung adenocarcinoma were selected; these patients were matched for gender, stage of disease at presentation, and definitive therapy modality to assess survival differences more accurately. Data regarding exposure to second-hand smoke were not collected secondary to lack of documentation in the charts reviewed. RESULTS: There were no significant differences between the 2 groups with regard to the overall survival rate (P = 0.34) or time to progression (P = 0.43). Smoking status (current vs. former vs. never-smoker) was not found to be predictive of survival in either the younger group (P = 0.51) or the older group (P = 0.92). CONCLUSIONS: The data from the current study indicate that overall survival and disease free survival rates were not significantly different in these two groups. Thus, the younger patient population should be treated similarly to the older patient population. However, a surprisingly high percentage of younger patients were female (45%) and had never smoked (27%), suggesting that risk factors other than active smoking may be involved in lung carcinogenesis in these patients.

Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer.

PURPOSE: To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC and abnormal p53 function were enrolled onto cohorts receiving escalating dose levels of Adp53 (1 x 10(6) to 1 x 10(11) plaque-forming units [PFU]). Patients were administered intravenous cisplatin 80 mg/m(2) on day 1 and study vector on day 4 for a total of up to six courses (28 days per course). Apoptosis was determined by the terminal deoxynucleotidyl- transferase-dUTP nick-end labeling assay. Evidence of vector-specific sequences were determined using reverse-transcriptase polymerase chain reaction. Vector dissemination and biodistribution was monitored using a series of assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent assay, vector-specific polymerase chain reaction assay, and antibody response assay). RESULTS: Twenty-four patients (median age, 64 years) received a total of 83 intratumor injections with Adp53. The maximum dose administered was 1 x 10(11) PFU per dose. Transient fever related to Adp53 injection developed in eight of 24 patients. Seventeen patients achieved a best clinical response of stable disease, two patients achieved a partial response, four patients had progressive disease, and one patient was not assessable. A mean apoptotic index between baseline and follow-up measurements increased from 0.010 to 0.044 (P =.011). Intratumor transgene mRNA was identified in 43% of assessable patients. CONCLUSION: Intratumoral injection with Adp53 in combination with cisplatin is well tolerated, and there is evidence of clinical activity.

Lymph node micrometastases in non small-cell lung cancer: clinical applications.

A large number of patients are diagnosed every year with non small-cell lung cancer, and their prognosis and response to treatment are inversely correlated to tumor stage at initial diagnosis. Despite the surgical removal of all apparent malignancy from patients with early disease, many will relapse, presumably as a result of disease that was undetected at initial evaluation. In an effort to identify those patients who have early lymph node involvement by metastatic disease, several groups of investigators have searched for the presence of micrometastases in hematoxylin-eosin-negative lymph nodes using immunohistochemical or molecular methods. Four of six groups of investigators using immunohistochemistry have found a significant incidence of lymph node micrometastases and a direct correlation between the absence of micrometastases and disease-free survival; these are encouraging results that require confirmatory studies. Molecular methods may potentially offer increased sensitivity; however, their high cost and the requirement to process large numbers of samples limits their use to research settings at present.

Docetaxel in the treatment of non-small cell lung cancer: review of single-agent trials.

Several phase II studies have evaluated docetaxel, administered as a 1-hour intravenous infusion at a dose of 100 mg/m2 every 3 weeks, for chemotherapy-naive patients with advanced non-small cell lung cancer. Results have been consistent across numerous trials, with an overall response rate in the range of 23% to 38% and a median survival of 9 months. Results of a multicenter phase III trial of docetaxel versus best supportive care for the first-line treatment of non-small cell lung cancer are pending. In the second-line setting, after failure of first-line platinum-based chemotherapy, four phase II studies of docetaxel 100 mg/m2 have achieved response rates ranging from 16% to 22%, with encouraging median survival times of 30 to 42 weeks. Preliminary results of a large, multicenter, randomized phase III trial also indicated an advantage for docetaxel over control with regard to response, time to progression, survival, and quality of life. Results of a multicenter phase III trial of docetaxel versus best supportive care as second-line treatment will be reported soon. Weekly docetaxel has been well tolerated in phase I studies, with dose-limiting toxicity being asthenia rather than myelosuppression. Phase II trials of a dosage of 36 mg/m2/wk in elderly patients with advanced non-small cell lung cancer are ongoing. Docetaxel is a potent radiosensitizer. The dose-limiting toxicity of docetaxel when administered weekly with concurrent chest radiation at 50 to 64 Gy is esophagitis. Phase II trials of weekly docetaxel plus concomitant chest radiotherapy are in progress at the recommended phase II dosage of 20 to 30 mg/m2/wk.

Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma.

PURPOSE: The combination of cisplatin, etoposide, and paclitaxel was studied in patients with extensive small-cell lung cancer in a phase I component followed by a phase II trial to determine the maximum-tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates. PATIENTS AND METHODS: Forty-one patients were treated between October 1993 and April 1997. Doses for the initial cohort were cisplatin 75 mg/m(2) on day 1, etoposide 80 mg/m(2)/d on days 1 to 3, and paclitaxel 130 mg/m(2) on day 1 over 3 hours. Cycles were repeated every 3 weeks for up to six cycles. The MTD was reached in the first six patients. In these six patients and in the next 35 patients, who were entered onto the phase II trial, response and survival were estimated. RESULTS: At the initial dose level, one of six patients developed febrile neutropenia, and five of six achieved targeted neutropenia (nadir absolute granulocyte count, 100 to 1,000/microL) without any other dose-limiting toxicity, defining this level as the MTD. Grade 4 neutropenia was observed in 88 (47%) of 188 total courses administered at or less than the MTD. Neutropenia was associated with fever in only 17 (9%) of 188 courses, but two patients experienced neutropenic sepsis that was fatal. Nonhematologic toxicity greater than grade 2 was observed in 10 (5%) of 188 total courses, with fatigue, peripheral neuropathy, and nausea/vomiting most common. The overall objective response rate was 90% of 38 assessable patients: six complete responses (16%) and 28 partial responses(74%). Median progression-free and overall survival durations were 31 and 47 weeks, respectively. CONCLUSION: The combination of cisplatin, etoposide, and paclitaxel produced response and survival rates similar to those of other combinations and was well tolerated.

Overview of docetaxel (Taxotere) in the treatment of non-small cell lung cancer.

In four initial phase II studies of docetaxel administered as a 1-hour intravenous infusion at a dose of 100 mg/m2 every 3 weeks in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC), the overall response rate was 31% in 128 evaluable patients and the median survival was 9 months. Five subsequent phase II studies of 100 mg/m2 docetaxel in the first-line setting showed similar results, with response rates in the range of 25% to 63% and favorable survival. Lower doses also have been evaluated in two trials using docetaxel 60 and 75 mg/m2, with overall response rates of 25% and 19%, respectively. In the second-line setting, after failure of first-line platinum-based chemotherapy, four studies of docetaxel 100 mg/m2 have achieved response rates of 16% to 22% and encouraging median durations of survival of 30 to 42 weeks. In both first-and second-line settings, the toxicity of docetaxel is tolerable. Docetaxel is clearly an active drug in both the first- and second-line treatment of NSCLC, and recently conducted phase III trials will further define the role of this agent in the standard treatment of NSCLC.