Thymidine phosphorylase expression is associated with time to progression in patients receiving low-dose, docetaxel-modulated capecitabine for metastatic breast cancer.

BACKGROUND: Preclinical data have indicated a synergistic interaction between docetaxel and capecitabine by means of taxane-induced up-regulation of thymidine phosphorylase (TP). On the basis of such premises, we conducted a phase II trial to determine the activity and tolerability of weekly docetaxel plus capecitabine in patients with metastatic breast cancer (MBC). Furthermore, we explored the relationship between TP tumor expression and benefit from this regimen. PATIENTS AND METHODS: Patients received docetaxel 36 mg/m(2) i.v. on days 1, 8, and 15 and capecitabine orally 625 mg/m(2) b.i.d. from days 8 to 21. Cycles were repeated every 4 weeks. In the correlative study, we evaluated the TP expression by immunohistochemistry and the TP messenger RNA expression by real-time RT-PCR in the primary tumor. RESULTS: Forty-seven women were enrolled. In the intention-to-treat analysis, objective responses were achieved in 24 patients (51%). Fourteen additional patients (30%) had stable disease. The median time to progression (TTP) was 6 months (range 1-44 months). Median survival was 17 months (range 1-48 months). Overall, the treatment was well tolerated. The most common clinical adverse events (all grades) were alopecia (55%), nail changes (53%), fatigue/asthenia (51%), nausea/vomiting (51%), neutropenia (49%), and neuropathy (49%). A significantly higher TTP was observed in patients with TP-positive tumors (log-rank test, P = 0.009). Interestingly, a subgroup analysis confirmed this TTP benefit in patients with TP-positive tumors obtaining a tumor response (log-rank test, P = 0.03), whereas the statistical significance was lost in nonresponders (log-rank test, P = 0.3). CONCLUSIONS: This study indicates that a regimen with low doses of capecitabine plus weekly docetaxel is active against MBC. The correlative analysis provides preliminary evidence that TP expression may be a predictive marker for therapeutic benefit.

Innovative schedule of oral idarubicin in elderly patients with metastatic breast cancer: comprehensive results of a phase II multi-institutional study with pharmacokinetic drug monitoring.

BACKGROUND: To determine if protracted low-dose oral idarubicin (IDA), feasible in a previous dose-finding study, would result in similar activity and a better toxicity profile in patients with metastatic breast cancer. PATIENTS AND METHODS: Elderly women (> or=65 years) with metastatic breast carcinoma were treated with 7.5 mg/day for 21 consecutive days, every 4 weeks. After the first fourteen patients, due to excessive toxicity, the protocol was amended to 5 mg/day. IDA and Idarubicinol (IDOL) plasma concentrations (C(trough)) were investigated in all patients. RESULTS: Between April 1999 and June 2004, 47 elderly patients were accrued in this two-part study (14 and 33 patients respectively). The median age was 74 and 75 years respectively. Visceral involvement was present in most patients. A partial response was noted in 7/31 patients (22%; 95% CI, 9.6-41.1%). Eleven patients had stable disease (33%). At the dose of 5 mg/day the treatment was well tolerated. Neutropenia grade 4 was present in only 6% of patients; alopecia > grade 1 and cardiotoxicity did not occur. The median time to progression was 3 months and the median overall survival was 17 months. IDA C(trough) and IDOL C(trough) levels were significantly associated with haematologic toxicity. CONCLUSION: This study shows that idarubicin at the dose of 5 mg/day for 21 consecutive days is feasible and effective in elderly breast cancer patients but do not demonstrate an improvement in efficacy. A determination of the IDA and IDOL plasma levels (C(trough)) is predictive for toxicity.

Treatment of older breast cancer patients with high recurrence risk.

Adjuvant treatment of elderly women affected by breast cancer who have a high risk of recurrence is one of the most questionable issues in clinical oncology. The use of tamoxifen in women with hormone receptor-positive tumors is a relatively simple therapeutic option considering the favourable toxicity profile, whereas the administration of adjuvant chemotherapy is more complicated and a variety of aspects need to be considered. The estimated life expectancy, the presence and degree of comorbid conditions, the geriatric assessment and estimated benefit from treatment should be taken into account. Due to the lack of data from clinical trials in women over the age of 70, the approach is still experimental. Clinical trials evaluating the role of adjuvant chemotherapy in high risk patients are currently being developed and hopefully in the near future, more convincing data on the best drugs, regimens and benefits for the treatment of elderly breast cancer patients will become available.

Fourteen-day infusion of ifosfamide in the management of advanced breast cancer refractory to protracted continuous infusion of 5-fluorouracil.

AIMS AND BACKGROUND: Ifosfamide is an active drug in advanced breast cancer. Short-term continuous infusion schedules have been evaluated with encouraging results. The aim of the study was to evaluate in patients with advanced breast cancer a 14-day infusion schedule previously tested at our center in soft tissue sarcomas. METHODS: From July 1998 to February 2000, 26 consecutive patients with heavily pretreated breast cancer, progressing during protracted continuous infusion of fluorouracil, were treated with ifosfamide at the dose of 800 mg/m2/day for 14 consecutive days by means of an elastomeric pump via an in-dwelling Groshong catheter. The median age of the patients was 52 years (range, 32-67) and median PS was 1 (range, 1-3). All patients were pretreated with anthracyclines or taxanes; the median number of chemotherapy lines in the metastatic phase was 2 (range, 1-4). Predominant metastatic sites wen soft tissues in 5 patients, lung in 6, liver in 7 and serosal cavities in 3. RESULTS: Twenty-four patients were assessable for response Two complete responses and 2 partial remissions were noted for an overall 16.6% response rate. The duration of response was 3+, 5, 8 and 10 months, respectively. Stabilization or mi nor response was observed in 2 more patients. The main tox ic effect was myelosuppression (grade 1-2 in 15 patients grade 3-4 in 4). Other toxicities included nausea in 14 patients (grade 3 in 2) and grade 1-2 vomiting in 2 patients. Hair lost or alopecia was universal. CONCLUSIONS: The regimen yielded some clinically useful re sponses with acceptable toxicity. Its evaluation in less ad vanced cases appears to be warranted.

Determination of tamoxifen and its metabolites in the endometrial tissue of long-term treated women.

Concentrations of tamoxifen and its metabolites were analysed in the endometrium of 23 post-menopausal asymptomatic breast cancer patients who were on chronic tamoxifen therapy. Small endometrial samples were collected during diagnostic hysteroscopy. Analysis of both serum and tissue for these compounds was performed by mass spectrometry. Tamoxifen and its metabolites were far more concentrated in the endometrium than in serum; tamoxifen was also significantly more concentrated in endometrium with hyperplastic changes than in atrophic endometrium. Endometrial polyps of an additional 9 women showed a trend to a lesser concentration of compounds. Increased concentration of tamoxifen compounds could possibly be explained by the avidity of these compounds for oestrogen receptors (ER).

Combination chemotherapy with navelbine and continuous infusion of 5-fluorouracil in metastatic, chemotherapy refractory breast cancer.

BACKGROUND: The protracted continuous infusion (PCI) of 5-fluorouracil (5-FU) has proven in several studies an active and well tolerated treatment for advanced, pretreated breast cancer. Navelbine has also activity in this setting. PATIENTS AND METHODS: Heavily pretreated patients with metastatic breast carcinoma were eligible for the study. Treatment consisted of 5-FU 250 mg/m2 given as a PCI by an elastomeric pump and navelbine 20 mg/m2 on days 1 and 8, every four weeks. Eighty-three patients (median age 54 years; range 32-82 years) entered the study. The median number of metastatic tumour sites was 2, with visceral involvement in 56 patients. Apart from five patients with contraindications, all patients had been pretreated with anthracyclines. Thirty-one patients had received taxanes and seventy-four bolus 5-FU. RESULTS: A median of 5 cycles (range 1-14) per patient was administered. The median duration of 5-FU infusion was 17 weeks (range, 4-90). In the 80 evaluable patients (3 not yet evaluable) 12 complete remissions and 24 partial remissions occurred (response rate, 45%). Median duration of response was 9 months. Toxicity was mild. Median survival was 20 months. CONCLUSIONS: PCI-5-FU combined with navelbine offers a reasonable chance of tumour regression with modest side effects in patients with heavily pretreated breast cancer.

Continuous infusion fluorouracil in the management of advanced breast cancer: a phase II study.

AIMS AND BACKGROUND: The evaluation of unconventional schedules of well-known drugs represents a promising avenue in the search for new regimens with a better therapeutic index in metastatic breast cancer. In particular, protracted continuous infusion (PCI) of 5-fluorouracil (5-FU) has yielded interesting results in gastrointestinal malignancies and in breast cancer. METHODS: From March 1996 30 consecutive patients with heavily pretreated breast cancer were treated with PCI 5-FU at a daily dose of 250 mg/m2 by means of disposable elastomeric pumps until progression or toxicity. The median age was 54 years (range, 28-71) and median performance status was 1 (range, 0-3). All patients but four were pretreated with anthracycline-containing regimens or taxanes; the median number of chemotherapy lines was 3 (range, 2-4). Metastatic sites were predominantly visceral in 60% of the patient population. RESULTS: All 30 patients were evaluable for response and toxicity. The median duration of PCI was 20 weeks (range, 2-36 weeks). Two complete responses (7%) and eight partial remissions (26%) were observed, giving an overall response rate of 33%. The median duration of response was six months (range, 4-9 months). Stabilization was observed in seven patients (23%) with a median duration of seven months (range, 3-9 months). The main toxic effects were grade I-II mucositis and hematologic toxicity, while grade 3 hand-foot syndrome was observed in eight patients (27%). CONCLUSIONS: This study confirms the efficacy and safety of 5-FU at this dosage and schedule in heavily pretreated women with advanced breast cancer. In order to improve on these results further studies are needed in a less advanced stage of the disease and together with other active drugs.

BRCA1 and BRCA2 genes: role in hereditary breast and ovarian cancer in Italy.

The heritable defects of BRCA1 and BRCA2 genes have been shown to predispose to breast and ovarian cancers. In a previous report, we analyzed 46 Italian families with breast and/or ovarian cancer for BRCA1 mutations. In the present study, those families and 11 others were screened for BRCA2 mutations; the newly enrolled families were also analyzed for the BRCA1 gene. The coding region and splice boundaries of BRCA2 and BRCA1 genes were assessed by the protein-truncation test and single-strand conformational polymorphism. A total of 20 different mutations were found in 21 families (37%). A total of 9 families (16%) showed mutations in the BRCA1 gene, including the one new mutation identified in this study (5382insC), and 12 families (21%) presented mutations in the BRCA2 gene. BRCA2-mutated families presented breast and ovarian cancers or breast cancers only, whereas most BRCA1-mutated families presented ovarian cancer alone or in association with breast cancer. All the BRCA2 mutations led to a truncated protein: 6 were frameshift mutations, 4 were non-sense mutations and 2 involved the intronic invariant region leading to splice variants. Therefore, in the Italian population, the cumulative proportion of BRCA1 and BRCA2 mutations was within the range observed in other studies (37%), with higher involvement of BRCA2 than of BRCA1. Many families in which no mutations were found presented a very high incidence of breast and/or ovarian cancer. Among the 36 BRCA1 and BRCA2 wild-type families, 24 presented at least 4 cancer cases, indicating the existence of other important predisposing genes.

Low incidence of BRCA1 mutations among Italian families with breast and ovarian cancer.

Most familial breast or ovarian cancers are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. The cloning of these genes has opened a new era for the genetic counseling of women with a family history of breast or ovarian cancer. To estimate the incidence of detectable BRCA1 mutations and to define the eligibility criteria for genetic testing in the Italian population, a total of 53 patients belonging to 46 families clustering multiple cases of breast and/or ovarian cancer were investigated. Seven families presented with ovarian cancer only, 16 had both ovarian and breast cancers, and 23 were characterized by breast cancer only. Using a combination of protein truncation test (PTT) and single strand conformational polymorphism (SSCP) analysis followed, when necessary, by direct sequencing, we found 8 distinct mutations, 2 of these not reported before. Five frameshift and 2 nonsense mutations led to a truncated protein. One mutation was a missense substitution involving a cysteine in the zinc finger domain. One variant creating an ETS binding site in intron I was found but its role was not defined. The percentage of families carrying mutations was 17%. Among the families characterized by ovarian cancer only and by breast and ovarian cancer, the percentage of BRCA1 mutations was 57% and 12.5%, respectively. In contrast, the percentage of altered BRCA1 in families with only breast cancers was 9%. In the 46 Italian families studied, BRCA1 mutations were detected in fewer kindreds than those previously hypothesized based on linkage analysis, especially when these were characterized by breast cancers only. Our results indicate that families with a low number of cancer patients should be referred for BRCA1 genetic testing mainly when ovarian cancer is present.

Tamoxifen as adjuvant after surgery for breast cancer and tamoxifen or placebo as chemoprevention in healthy women: different compliance with treatment.

AIM: The aim of this study was to investigate whether tamoxifen toxicity and treatment discontinuations differed in the adjuvant versus chemopreventive setting. METHODS: At our Institutions 119 postmenopausal breast cancer patients were randomized from August 1987 to March 1995 to tamoxifen only within adjuvant studies (International Breast Cancer Study Group studies VII and IX) and 202 healthy hysterectomized women aged 35-70 years were randomized from November 1993 to May 1996 in a multicenter, double-blind, placebo-controlled chemoprevention study (Italian Tamoxifen Prevention Study). The tamoxifen dose was 20 mg/day for 5 years in all studies. Median age was 66 years (54-85) in the adjuvant studies and 53 years (37-69) in the chemoprevention study. Median treatment duration was 238 and 120 weeks, respectively. RESULTS: Patients treated within adjuvant studies experienced more hot flashes, vaginal discharge and/or bleeding, bone marrow depression and weight gain than those treated in the chemoprevention study, consistent with the fact that a proportion of women in the latter study were receiving placebo. Temporary discontinuation occurred in 2.5% of patients in the adjuvant studies and in 5.4% of women in the chemoprevention study (difference not statistically significant). Permanent discontinuation was more frequent in the chemoprevention study than in the adjuvant ones (26.7% vs 15.1%--P< 0.05). CONCLUSIONS: In summary, our data show that, although the toxicity of tamoxifen is superimposable in the two settings, a larger proportion of women treated as chemoprevention discontinue treatment spontaneously. Due to the double-blind nature of the chemoprevention study, the impact of the toxicity of tamoxifen upon compliance in the chemopreventive setting cannot be ascertained.

Does the information level of cancer patients correlate with quality of life? A prospective study.

AIMS AND BACKGROUND: The aim of the study was to evaluate the impact of information level on quality of life in cancer patients previously studied for their information level. PATIENTS AND METHODS: The information level was determined by means of a questionnaire that explored the degree of information on diagnosis and status of disease, the patient's interpretation of his/her disease status, and his/her satisfaction with the information received. Quality of life was evaluated, some months after evaluation of the information level, by means of the Functional Living Index for Cancer (FLIC) and the State-Trait Anxiety Inventory (STAI 1-2). RESULTS: A total of 175 patients were studied. Information was adequate in 53.7% of patients. An adequate level of information was present more frequently among patients aged < or = 65 years and in those patients followed at a cancer institute. There was no difference in the quality of life of adequately versus inadequately informed patients. Satisfaction with the information received influenced quality of life in both age groups. Objective clinical variables (active disease present and ongoing treatment) negatively affected quality of life in patients <65 years, whereas the subjective perception of the presence of disease was associated with a worse quality of life in older patients. CONCLUSIONS: In the study, although the level of information did not affect the quality of life, satisfaction with the information was associated with a better quality of life. The finding stresses the importance of a sensible disclosure of diagnosis and prognosis.

Vinorelbine treatment of advanced non-small cell lung cancer with special emphasis on elderly patients.

The aim of this study was to investigate the activity and the toxicity of vinorelbine (VNB) in a population of patients with locally advanced inoperable or metastatic non-small cell lung cancer (NSCLC) including elderly patients unfit for cisplatin-based chemotherapy. VNB was administered at a dose of 25-30 mg/m2, intravenously, weekly until progression. Of the 83 patients who entered the study (median age 63 years, number of patients aged > or = 70 years = 23, median performance status = 80, stage IV in 58 patients, previous chemotherapy in 15 patients), 76 were evaluable. One complete remission and 22 partial remissions were noted (30.2% response rate). Toxicity was mild. Median survival was 9 months. No effect of age upon outcome was detected. Thus, single agent VNB is a reasonable option for advanced NSCLC, particularly in elderly patients.

Cisplatin and etoposide versus cyclophosphamide, epirubicin and vincristine in small cell lung cancer: a randomised study.

From September 1986 until December 1991, 139 patients with histologically-proven small cell lung cancer, age < 75 years, performance status > 40, absence of brain metastases and no previous treatment, were randomised to receive either CEV cyclophosphamide 1000 mg/m2 intravenous (i.v.), epirubicin 70 mg/m2 i.v., vincristine 1.2 mg/m2 i.v., every 3 weeks or PE (cisplatin 20 mg/m2 i.v. and etoposide 75 mg/m2 i.v. for 5 consecutive days, every 3 weeks) for six cycles. After three cycles, responding patients received radiotherapy to the chest (45 Gy/15 sessions) and to the brain (30 Gy/10 sessions--only in patients with limited disease achieving complete remission). 3 patients were ineligible. Patient characteristics included (CEV/PE) total number 66/70, median age 60/61 years, median performance status 80/80, extended disease 33/48 cases (P = 0.04). In evaluable patients, 42/62 (67.7%) responded to CEV while 42/58 (72.4%) responded to PE (P = non-significant); respective complete response rates were 16.1 and 29.3% (P = non-significant) and respective complete response rates in patients with extended disease were 9.4 and 28.9% (P = 0.03). Median survival was 10.5 months, without significant differences in the two treatment arms, even after adjustment for stage. PE was less well tolerated than CEV. Although PE is more active than CEV in certain subsets of patients, its apparent inability to improve survival in this and in other studies questions its routine use in small cell lung cancer.

Treatment of malignant mesothelioma with epirubicin and ifosfamide: a phase II cooperative study.

From May 1988 to March 1990, 17 consecutive patients with histologically proven malignant mesothelioma were treated with epirubicin 75 mg/sqm i.v. on day 1 and ifosfamide 1.8 gr/sqm/day i.v. from day 1-5. Treatment was repeated every 3 weeks until progression. Fifty-three chemotherapy cycles were administered to the 17 patients treated (median, 3 cycles/patient). No complete responses, 1 partial response, 8 stable diseases and 8 progressions were noted. Toxocity was acceptable and no treatment-related deaths occurred. Actuarial median survival was 6 months. In this study, a combination of full doses of epirubicin and ifosfamide did not prove to be active in malignant mesothelioma.

Epirubicin in the treatment of malignant mesothelioma: a phase II cooperative study. The North-Eastern Italian Oncology Group (GOCCNE)--Mesothelioma Committee.

From September 1986 to April 1988, all consecutive patients with histologically proven (pathologic review mandatory) malignant mesothelioma, measurable disease, age less than 75 years, Karnofsky performance status equal to or greater than 40, and no previous chemotherapy were treated with epirubicin at the dosage of 75 mg/m2 i.v. every 3 weeks. Of the 23 patients who entered the study, 2 were retrospectively found not to have malignant mesothelioma. In the 21 eligible patients (all evaluable), no complete remission, 1 partial remission, 11 stable diseases and 9 progressions were noted. Toxicity was very mild. Median survival was 7.5 months. At the dosage used, epirubicin proved to be of little value in the management of these patients. Whether higher doses are more effective, as has been noted in other tumors, remains to be ascertained.

Buserelin treatment of advanced prostatic cancer: a phase II study.

From August 1986 to September 1988, 76 eligible patients with advanced prostatic carcinoma, measurable or evaluable disease, no previous hormonal treatment, were treated with Buserelin at a dosage of 500 micrograms every 8 h for 7 days, followed by 400 micrograms intranasally three times a day. No concomitant antiandrogens were administered. In the 63 evaluable patients (11 patients not yet evaluable because of short treatment time, two lost to follow-up), three complete remissions, 28 partial remissions, 30 stable disease and two progressions were obtained (National Prostatic Cancer Project criteria). Median duration of response was 55+ weeks. Side effects were modest, mostly related to the endocrinological effects of Buserelin. Transient increase in serum testosterone levels was found in 37% of the evaluable patients, but transitory 'flare-up' was present in seven patients only. With a median follow-up time of 11.5 months, median survival has not been reached. In conclusion, this study confirmed the activity of Buserelin and the feasibility of its middle-term administration.

Combination chemotherapy with cisplatin and etoposide associated with radiotherapy in the treatment of small-cell lung cancer.

A total of 52 consecutive, previously untreated patients with small-cell lung cancer (SCLC) were scheduled to receive six cycles of a combination of etoposide (75 mg/m2 per day) and cisplatin (20 mg/m2 per day), each cycle given over 5 consecutive days. In all, 28 patients had extensive disease (ED) and 24, limited disease (LD). After three cycles of chemotherapy, all responding patients were given chest radiotherapy (RT) (45 Gy in two split courses and 30 Gy in LD and ED, respectively); only patients with LD who achieved complete remission (CR) after three cycles of chemotherapy were given prophylactic brain irradiation (30 Gy). In the 51 evaluable patients, the overall response rate was 90%, with a 31% CR and a 59% partial remission (PR) rate. In LD and ED patients, 57% and 11% CR rates and 30% and 82% PR rates were noted, respectively. Myelosuppression was the most frequently observed toxicity. The median duration of response was 12 months in LD (range, 3-41 + months) and 7 months (range, 2-12 months) in ED; the median survival was 15 months in LD and 9.3 months in ED, respectively. In all 30% of LD patients are alive and well at a minimal follow-up of 18 months. This trial confirms the activity of the cisplatin-etoposide combination in SCLC.

Presurgery chemotherapy (CT) in locally advanced bladder carcinoma: a feasible and possibly effective approach.

In October 1984, a prospective pilot study aiming to evaluate the feasibility and to preliminarily test the efficacy of the chemotherapy--surgery sequence in locally advanced bladder carcinoma was started at our institutions. Chemotherapy consisted of adriamycin 50 mg mq-2 and cisplatin 50 mg mq-2 on day 1 and fluorouracil 500 mg mq-2 and teniposide 100 mg mq-2 on days 1 and 8; chemotherapy was repeated every 3 weeks for three cycles and followed by surgery (radical cystectomy; TUR if radical surgery medically contraindicated). The characteristics of the 28 patients so far treated include: T3b in 26 patients, local relapse after surgery in two, nodal metastases in seven. Twenty-five patients were male and three female, median age was 61 yr (range 42-75). Clinical response following chemotherapy was: complete remission (CR) in five patients, partial remission (PR) in 15, stable disease (SD) in three, progression (PRO) in two. Three patients are not evaluable. Treatment was moderately well tolerated. Thirteen patients underwent radical surgery, three exploratory surgery, three TUR; refusal in three patients, early death in two, too early in one. No evidence of disease was found in the surgical specimen of five patients (three CR, two PR), microscopic residual disease in four PR patients, gross residual disease in 11 patients (one CR, six PR, two SD, two PRO). Actuarial median survival (all 28 patients) is 45% at 36 months. These preliminary results suggest that the combination of chemotherapy and surgery is feasible and may be effective in these poor prognosis patients.

Chemotherapy of advanced non-small-cell lung cancer with cyclophosphamide, adriamycin, methotrexate, and procarbazine versus cisplatin and etoposide. A randomized study.

All consecutive eligible patients with non-small-lung carcinoma seen at Centro di Riferimento Oncologico and Istituto Nazionale per la Ricerca sul Cancro were entered into a randomized chemotherapy study. Conditions of eligibility included advanced stage (stage III not amenable to radiation therapy or i.v.), measurable or evaluable lesions, age less than 70 years, performance status (PS) greater than 40, and no previous chemotherapy. Patients were randomized to either CAMP (cyclophosphamide 300 mg/m2 i.v., adriamycin 20 mg/m2 i.v., methotrexate 15 mg/m2 i.v. days 1 and 8, procarbazine 100 mg/m2 orally from day 1 to day 10, every 4 weeks) or DE (cisplatin 20 mg/m2 i.v. for five consecutive days and etoposide 75 mg/m2 i.v. on the same days, every 3 weeks). Treatment was continued until progression. Out of the 136 patients randomized, 133 were eligible (CAMP 62, DE 71) and 108 evaluable. Patient characteristics included male/female ratio 57/5 (CAMP) and 61/10 (DE), median age of 60 years (CAMP) and 59 years (DE), PS greater than or equal to 70 for 39 (CAMP) and 50 (DE), PS less than 70 for 23 (CAMP) and 21 (DE), stage III for 18 (CAMP) and 15 (DE), and stage IV for 44 (CAMP) and 56 (DE). DE was superior to CAMP in terms of response rate, defined as responding/evaluable patient ratio (38.2% versus 20.8%); however, the responding/eligible patient ratio was not significantly different in the two groups. The superiority of DE tended to be more marked in stage III patients, in patients with PS greater than or equal to 70, and in the squamous histological type. Toxicity was acceptable (one toxic death) and evenly distributed in the two treatment groups; only renal toxicity was prevalent in the DE group. Survival (all eligible patients) was significantly better in the DE than in the CAMP group. Whether DE chemotherapy is superior to a no-chemotherapy approach has not been evaluated in this study and remains to be determined.