Intraoperative radiation therapy on pancreatic cancer patients: a review of the literature.

Pancreatic cancer is rarely curable, and the overall survival rate at 5 years is under 4%. This study aimed to assess the efficacy, effectiveness and safety of intraoperative radiation therapy (IORT) as treatment in pancreatic cancer, by means of a systematic review of the literature. We searched Pubmed from 1980 until 2010 by means of prospective randomized trials. The aim was to assess the potential impact of IORT on local control, quality of life and overall survival. The search was restricted to articles published in English. IORT offers the opportunity to administer high doses of irradiation to areas of neoplastic involvement while attempting simultaneously to spare normal tissues in the region from potentially damaging radiation exposure. However, the results were not in favour of IORT in the case of pancreatic cancer in locally advanced and metastatic stages. There is no clear evidence to indicate the IORT as more effective than other therapies in treating pancreatic cancer.

Hypoxia inducible factor (HIF-1a and HIF-2a) expression in early esophageal cancer and response to photodynamic therapy and radiotherapy.

Hypoxia inducible factor 1a and 2a (HIF-1a and HIF-2a) are key proteins regulating cellular response to hypoxia. Because the efficacy of photodynamic therapy (PDT) is dependent on the presence of oxygen, the assessment of HIF-1a and HIF-2a expression may be of value in predicting clinical response to PDT. Using recently produced MoAbs, we examined the expression of HIF1a and HIF2a in a series of 37 early-stage esophageal cancers treated with PDT and with additional radiotherapy in case of incomplete response after PDT. Strong expression of the HIF1a and of HIF2a proteins in all optical fields examined was noted in 51% and in 13% of cases, respectively. High expression was associated with a low complete response (CR) rate and with the absence of bcl-2 protein expression. On the contrary, bcl-2 expression was associated with a high CR rate. Combined analysis of HIF1a and bcl-2 protein expression revealed that of 16 cases with high HIF1a expression and the absence of bcl-2 reactivity, only 1 (7%) responded completely to PDT (P = 0.007). Bivariate analysis showed that HIF1a expression was independently related to response to PDT (P = 0.04; t ratio = 2.8), whereas bcl-2 approached significance (P = 0.07; t-ratio = 1.8). The final response to radiotherapy was high (70%) and independent of the HIF and bcl-2 status, which may be a result of reoxygenation after cellular depletion mediated by PDT. The present study suggests that assessment of HIF and of bcl-2 expression are important predictors of in vivo sensitivity to PDT. Modulation of PDT response with bioreductive drugs and/or drugs targeting bcl-2 (i.e., taxanes) may prove of significant therapeutic importance in a subgroup of patients with high HIF expression.

Liposomal doxorubicin and conventionally fractionated radiotherapy in the treatment of locally advanced non-small-cell lung cancer and head and neck cancer.

PURPOSE: Stealth (ALZA Corporation, Palo Alto, CA) liposomal drug formulation allows a higher intratumoral accumulation and a prolonged plasma half-life of the encapsulated drugs. In the study presented here, we evaluated the feasibility of Stealth liposomal doxorubicin (Caelyx; ALZA Corporation) administered concurrently with conventionally fractionated radiotherapy in the treatment of non-small-cell lung cancer (NSCLC) and head and neck cancer (HNC). PATIENTS AND METHODS: Fifteen patients with NSCLC and 15 with squamous-cell HNC were recruited in two phase I dose-escalation trials. The starting dose of Caelyx was 10 mg/m(2) every 2 weeks (for three cycles during radiotherapy) and was increased by 5 mg/m(2) dose increments for every three patients. RESULTS: The maximum tolerated dose of Caelyx was 20 mg/m(2) for HNC and 25 mg/m(2) in NSCLC patients. Oral/pharyngeal mucositis was the dose-limiting toxicity for HNC patients. "In field" radiation skin toxicity was slightly increased. Hematologic toxicity was minimal. Single photon emission computed tomographic evaluation of Caelyx distribution, using technetium-99m-diethylenetriamine pentaacetic acid labeling, revealed a high intratumoral accumulation of the drug. The tumor to thoracic vessel area count ratio in the NSCLC cases ranged from 0.6 to 1.6 (mean +/- SD, 1.01 +/- 0.29), whereas this ratio was higher (0.8 to 1.85; mean +/- SD, 1.35 +/- 0.39) in HNC cases (P =.049). The complete response rate was 21% in the NSCLC cases and 75% in the HNC cases. NSCLC cases with higher Caelyx tumor accumulation responded better to the regimen. The tumor microvessel density assessed with the anti-CD31 monoclonal antibody directly correlated with the degree of the Caelyx accumulation (P =.007; r =. 92). CONCLUSION: We conclude that combination of radiotherapy with Stealth liposomal doxorubicin is feasible. The potential role of such a regimen in the treatment of highly angiogenic tumors requires further investigation.

Non-small cell lung cancer functional imaging: increased hexakis-2-methoxy-isobutyl-isonitrile tumor clearance correlates with resistance to cytotoxic treatment.

Detection of P-glycoprotein and other multidrug resistance protein activity is currently under investigation to identify subgroups of cancer patients with tumors resistant to chemotherapy. Application of a test that reliably evaluates the phenomenon in vivo would not only serve as a predictor for responses to chemotherapy but would also be of use in testing the efficacy of multidrug resistance reversers in humans. Tc-99m radiolabeled hexakis-2-methoxy-isobutyl-isonitrile (Tc-sestamibi) has been recently shown to be extruded from cells through P-glycoprotein activity. In the present study, we examined the uptake and extrusion rate of the radiotracer in 25 patients with advanced non-small cell lung cancer undergoing chest radiotherapy, using a novel scintigraphic technique based on simulation-guided pinhole imaging. Five-min tumor images were taken 10, 60, and 120 min postinjection of 20 mCi of Tc-sestamibi. Six of 25 (24%) of tumors showed a 1.3-1.7 times higher extrusion rate as compared to that of normal lung tissue. Increased tumor clearance of Tc-sestamibi significantly correlated with resistance to radiotherapy (P = 0.05) as well as the existence of distant metastasis (P = 0.008). Patients with known resistance to chemotherapy had a higher extrusion rate as compared to chemotherapy-naive patients (P = 0.01). Moreover, increased Tc-sestamibi tumor capture was seen in patients with distant metastasis (P = 0.09). We concluded that functional imaging of lung cancer with Tc-sestamibi may have a role in predicting responses to cytotoxic treatment and in identifying tumors with aggressive behavior. Additional clinicopathological trials are required to investigate whether Tc-sestamibi kinetics correlates with P-glycoprotein expression, intratumoral angiogenesis, or other mechanisms.

The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma.

PURPOSE: We evaluated the impact of overall treatment time on the disease-free survival (DFS) and local control after radiotherapy for nonsmall cell lung carcinoma. METHODS AND MATERIALS: One hundred fifty-three cases considered as responders to radiotherapy were retrospectively analyzed. Patients with Karnofsky status < 70, pretreated with chemotherapy and with pleural or pericardial effusion, were excluded from the analysis. Radiation dose homogenization was done with calculation of the normalized total dose without (NTD) and with time correction (NTD-T) for alpha/beta = 10 Gy. RESULTS: Kaplan-Meier curves for 2-year DFS showed that any analysis based on radiation dose can prove to be erroneous when the time factor is neglected. Although there was no difference between the 47-55 Gy and 56-64 Gy NTD groups, a log rank test revealed a strong difference (p < 0.0002) between NTD-T groups. No difference was observed for patients with mediastinal involvement. Logistic regression analysis showed a statistical association of dose on 2-year local progression-free probability for different time compartments. For those cases without mediastinal involvement, the daily dose lost because of treatment protraction beyond 20 days after the beginning of radiotherapy was estimated to 0.2 Gy/day. When all cases were considered together this was calculated to 0.45 Gy/day. CONCLUSION: Time factor should not be underestimated when evaluating the results of radiotherapy for nonsmall cell lung cancer. There is strong evidence that prolonged overall treatment time could be a major cause of the failure of radiotherapy to control the local disease.

A pilot study of the effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients during X-radiation therapy: a preliminary report.

PURPOSE: To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in reduction of radiotherapy-induced oral mucositis. METHODS AND MATERIALS: Seventeen patients who were going to be irradiated with a total dose of 50-70 Gy for head and neck malignancies were included in the study. After the second week of radiotherapy, with the experience of oral pain, GM-CSF 400 microg was administered locally, once a day, until completion of radiotherapy. Patients were evaluated weekly for mucosal reaction and functional impairment. RESULTS: Three patients with gross and functional mucositis grade I after the second week, completed the planned radiotherapy showing mucositis grade I. Eleven patients who experienced, after 2 weeks of radiotherapy, mucositis grade II and III, presented after the third week with gross mucositis grade I and II and functional impairment grade I. One of these 11 patients was then lost to follow-up and the remaining 10 completed their planned radiotherapy having an almost asymptomatic mucositis grade I. The 15th patient with gross mucositis grade III after the 2 weeks of radiotherapy, had a 2-day interruption because of painful mucositis and then continued and completed radiotherapy with gross and functional mucositis grade I. The 16th patient with mucositis grade III after the second week, did not show any improvement, and completed her planned radiotherapy with mucositis grade III which finally healed after the administration of acyclovir. The last, 17th patient discontinued radiotherapy at the third week because of mucositis grade IV and severe ulceration in apposition to an extensive gold prosthesis. CONCLUSION: The local administration of GM-CSF significantly reduced and almost healed radiation-induced oral mucositis in 14 of 17 patients during the radiotherapy, which was completed within the preplanned time and without any significant patient weight loss or functional impairment.

Outcome of patients receiving photodynamic therapy for early esophageal cancer.

PURPOSE: Photodynamic therapy (PDT) has shown remarkable activity in a variety of human cancers. In the present study, we report the effects of PDT on inoperable early-stage esophageal cancer. METHODS AND MATERIALS: Sixty-two patients were treated with an argon dye laser (630 nm wavelength, 300-800 mW of power, energy dose of 200-300 J/cm) after intravenous injection of 5 mg/kg of hematoporphyrin derivative. Eighteen patients (29.5%) had in situ carcinoma (Tis), 30 (48.5%) had T1-stage cancer, 7 (11%) had T2-stage cancer, and 7 (11%) had recurrent disease in the anastomotic area after previous surgery without evidence of invasion outside the lumen. Patients with residual disease after two rounds of PDT received definitive radiotherapy. Patients were evaluated for response to therapy and survival. The follow-up time ranged from 3 to 90 months (median, 32 months). RESULTS: The complete response (CR) rate was 37% (23 of 62) in patients who received PDT alone and 82% (51 of 62) in those who also received radiotherapy. The CR rate after PDT alone was statistically higher (p = 0.04) for patients who had Tis/T1 lesions (21 of 48; 44%) than for those with T2-stage disease (2 of 7; 28%) or recurrent tumors (0 of 7; 0%). Fifty-two percent of patients who had CR following PDT alone did not suffer local tumor recurrence. The median local progression-free survival times after PDT and additional radiotherapy (in cases with incomplete response) was 49 months for Tis- and T1-stage lesions, 30 months for those with T2-stage disease, and 14 months for patients with locally recurrent disease. Patients who completely responded to PDT had a median overall survival (OS) of 50 months, which was significantly longer (p < 0.003) than that of patients not responding to PDT. Toxicity was minimal; we recorded three cases of esophageal stenosis (7%) and one case of tracheo-esophageal fistula (2.5%) after combined PDT and radiotherapy. CONCLUSION: PDT is an effective regimen for early esophageal cancer, giving a CR rate of about 40%, long-term local control and favorable overall survival. Additional radiotherapy in cases of incomplete response to PDT is effective and potentially curative in another 45% of cases.

Clinical and experimental evidence of Bcl-2 involvement in the response to photodynamic therapy.

PURPOSE: The role of apoptosis related proteins in the response of human malignancies to photodynamic therapy (PDT) is under investigation. The aim of the study was to examine the role of p53 and of bcl-2 protein expression in the response to PDT. MATERIALS AND METHODS: Paraffin-embedded material from 37 patients with early esophageal cancer treated with PDT (argon dye laser after intravenous injection of hematoporphyrine derivative) was studied immunohistochemically for p53 protein nuclear accumulation and bcl-2 cytoplasmic expression. Patients with residual disease after two rounds of PDT received definitive radiotherapy. In a subsequent in vitro study, W138 human lung fibroblasts and W138-SV-40 virus transformed were assessed for their sensitivity to PDT. The constitutive bcl-2 overexpression of the transformed cells vs. normal cells (assessed with RT-PCR) was 16-fold. RESULTS: Positive bcl-2 and p53 expression was noted in 10 out of 36 (27%) and 14 out of 36 (39%) patients, respectively. Seven out of 11 tumors (63%) with bcl-2 expression responded completely to PDT vs. 6 out of 26 (23%) of cases with no bcl-2 expression (p = 0.02). No association of p53, T-stage and of histology grade with response to PDT or PDT/RT was noted. The sensitivity to PDT of transformed human fibroblasts compared to normal ones was 4 times more at a fluence of 4.3 J/cm2 (4% vs. 1% cell kill) as well as at a fluence of 5.4 J/cm2 (8% vs. 2% cell kill). CONCLUSION: Bcl-2 protein expression is associated with favorable response to PDT and can be used as a predictor of cancer response to PDT. This finding can be explained by experimental studies showing that PDT induces selective degradation of the bcl-2 protein, leading to apoptosis by decreasing the bcl-2/bax ratio. Studies on PDT combination with agents targeting bcl-2 (i.e. taxanes) are on going to eventually assess a super-additive effect.

Hypofractionated radiotherapy with 5-fluorouracil radiosensitization for locally "far advanced" breast cancer.

Seventeen patients who had locally far-advanced breast cancer were treated with hypofractionated radiotherapy (4-5 Gy/fraction, twice a week) and concomitant 5-fluorouracil (5-FU 300 mg/m2 intravenously, 1 hour before every radiotherapy fraction). Fourteen of the seventeen patients had disease that was not responding to chemotherapy. Early toxicity was low and none developed grade III/IV toxicity. Two of the seventeen patients showed moist skin desquamation and four of seventeen had grade II anemia. Of eight patients who survived longer than 12 months, symptomatic breast fibrosis was observed in one (12%), asymptomatic pericarditis in one (12%) and symptomatic radiation pneumonitis in one (12%). Plexopathy and arm edema grade II were observed in one patient and two patients, respectively. Quality of life substantially improved. Complete response was documented in five of the seventeen patients (29%), with pathologic confirmation in three. Seven of the seventeen (41%) patients were considered to be partial responders, four (23%) had a minimal response, and one (6%) progressed during treatment. Local progression-free survival (1-24 months) was achieved in 12 of 17 patients. Four of the seventeen (23%) patients are alive, with no evidence of disease (local or distant) 8 to 24 months after radiotherapy. Hypofractionated chemoradiotherapy with 5-FU is an effective, convenient, and well-tolerated regimen for far-advanced breast tumors.

Transurethral radiotherapy for benign prostatic hypertrophy-related urethral obstruction. Dosimetry, ethics, and preliminary results.

The aim of this study is to present our preliminary experience in treating BPH-related urine retention, resistant to other medical treatment, with transurethral brachytherapy. We also deal with dosimetric analysis so as to eliminate ethical concerns about the exposure of patients not suffering from cancer to a certain level of body irradiation. Patients suffering from BPH-related urethral obstruction were treated with two transurethral applications (three weeks apart) of Cs137 MDR, which delivered a total of 16 Gy, at 0.5 cm from the urethral walls (dose rate 5-7 Gy/h). The application was done under ultrasonographic observation. Dosimetric calculation of the radiation exposure of the human body during transurethral radiotherapy (TURT) was performed for patients suffering from prostate cancer and treated with external beam radiotherapy and a boost dose through transurethral brachytherapy. For this purpose we used TLDs on skin surface and dosimetric analysis of X-ray films. Five patients treated for BPH urethral obstruction presented no sign of acute toxicity. All of them were weaned of their indwelling catheter immediately after the end of the first application. Obstruction did not recur within 12-18 months of follow-up. The dose delivered outside the prostate ranges from 1-7 cG, depending upon location. Proximal rectal and bladder walls received 1-2 Gy, a dose that is far from inducing acute or late toxicity. The estimated risk for carcinogenesis is negligible, and the expected benefit for the quality of life transcends the risks. No ethical concern is justified for testing transurethral radiotherapy for BPH-related urethral obstruction. TURT seems to be effective and provides durable results. Further investigation is required.

Hypofractionated radiotherapy with concurrent 5-fluorouracil radiosensitisation for recurrent or locally advanced colorectal cancer. A phase II study.

In a pilot study we treated 19 patients suffering from recurrent or locally advanced inoperable colorectal cancer, with concurrent hypofractionated radiotherapy (4-5 Gy/fraction, 2 fractions per week) and 5-fluorouracil bolus, 1 hour before RT at doses of 300 mg/m2. For 16 patients treated with radical intent the Normalised Total Dose for alpha/beta = 10 Gy ranged between 56-74 Gy (median 62 Gy). The schedule used was very well tolerated. Moderate grade II haematological toxicity was observed in 11% of cases and diarrhoea grade II/III resulting in 2-4 weeks treatment delay was observed in 26% of cases. One case with bowel perforation and one with painful subcutaneous fibrosis was observed during 12-27 months of follow-up. Out of 16 patients treated with radical intent 4 (25%) showed complete response and the overall response rate was 56% (9/16). The one-year symptom-free survival was obtained in 11/16 (69%) radically treated patients. It is concluded that hypofractionated radiochemotherapy with 5-fluorouracil for recurrent or locally advanced colorectal cancer is an effective regimen and has acceptable acute and late toxicity. Further investigation is required.

Radiotherapy alone for non-small cell lung carcinoma. Five-year disease-free survival and patterns of failure.

One hundred and fifty-three patients with inoperable non-small cell lung cancer (NSCLC) treated with radiotherapy alone have been retrospectively analysed. Normalized Total Dose (NTD) as defined by Macejewski, TN-stage (AJC-system) and histology have been examined with respect to 5-year disease-free survival (DFS) and the patterns of failure so as to identify subgroups of patients that routinely should be treated with radical intent. The 5-year DFS for T1, 2-N0, 1 and T3-N0, 1 staged patients was 30% (7/23) and 25% (4/16) respectively when the tumor NTD (a/b = 10 Gy) was 56-64 Gy vs. 12% (5/41) and 0% (0/10) when the NTD was 48-55 Gy. This difference was statistically significant for the squamous cell histology group. The higher doses significantly altered the patterns of death in N0, 1 staged squamous cell carcinoma and adenocarcinoma patients. Forty-five percent (22/55) and 41% (12/29) of squamous cell and adenocarcinoma patients respectively, died from local relapse without evidence of distant metastases when NTD less tha 55 Gy were given vs. 21% (9/42) and 13% (2/15) when the NTD delivered was 56-64 Gy (p < 0.05). Although for N2, 3 staged patients or patients with direct extension of the tumor into the mediastinum death from local relapse occurred in 38% (10/26) of the high NTD treated patients vs. 51% (19/37) of the low-dose treated ones, the difference was not statistically significant. It is concluded that NSCLC patients should not à priori be considered as non-radiocurable. At least 30% of the patients with early local stages can be long-term disease-free survivors with radiation NTD up to 60 Gy and better results are to be expected with higher doses. Advanced T-stage without mediastinal involvement should be treated with radical intent since a high NTD could give cure rates of over 25%. The disappointing results for patients with mediastinal disease could perhaps be attributed to the low NTD delivered. For patients with good performance status, hyperfractionated regimens delivering high tumor doses should be tested and chemotherapy should be adapted to these radiation treatment schedules.

Transurethral 137Cs medium dose rate radiotherapy as a boost for small-sized localized prostatic carcinomas.

The aim of this study is to present preliminary experience with 137Cs medium dose rate (MDR) afterloading transurethral radiotherapy for small-sized (< 2.5 cm) prostatic carcinomas. The phase II protocol comprises 46 Gy of external beam radiotherapy, followed by two insertions (1 week apart) of 137Cs MDR transurethral brachytherapy, each one delivering 8 Gy to a point 0.5 cm from the urethral walls. The treatment is completed with a 14-Gy boost to the prostatic area through lateral external beam fields. Up to now, 9 patients have been treated. The transurethral insertion is a simple procedure, requires no anesthesia and the ultrasonographic observation precisely and easily guided the positioning of the applicator. All 9 patients are alive and disease-free 12-36 months after the end of radiotherapy. One of them presented a mild degree of urethral stricture and none developed chronic proctitis or cystitis. Seven patients were sexually potent before radiotherapy and all of them maintained their potency. Transurethral radiotherapy for prostatic carcinoma requires further investigation. The radiation dose that the procedure delivers to the prostate is higher than the one prescribed for external beam irradiation regimens. Rectal and bladder dose is substantially reduced. Although the prostatic urethra receives a higher dose, the incidence of urethral stricture is low probably because of the small tissue volume (8 cm3) in the high radiation dose area.

Concurrent hypofractionated radiotherapy and 5-Fluorouracil for advanced sarcomas of the bone.

Purpose. 5-Fluorouracil (5-FU) has shown radiosensitizing properties in vitro. This paper reports the effects of radiotherapy and concomitant intravenous 5-FU radiosensitization in the treatment of advanced bone sarcomas.Subjects/methods. Four patients with large inoperable bone sarcomas (three chondrosarcomas and one fibrosarcoma) were treated with hypofractionated radiotherapy and concomitant 5-FU bolus injection (300 mg m(-2)) before each fraction of radiotherapy. A radiation fraction of 5 Gy was given twice a week to a normalized total dose (alpha/beta=4 Gy) of 75 Gy.Results. The regimen was well tolerated, the main toxicity being grade I/II diarrhoea in two cases with pelvic irradiation. Treatment interruption for 1 week was necessary in two cases with pelvic disease but not in two patients treated for sarcoma of the extremities. A complete symptomatic relief was obtained in all cases immediately after the third to the fifth fraction and the median duration was 10 months. Computed tomography scan documented a partial response in 2/4 cases.Discussion. Hypofractionated radiotherapy combined with potential lethal damage inhibitors for bone sarcomas requires further investigation.

Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in non-small-cell lung cancer: impact on tumour neoangiogenesis and survival.

Angiogenesis is recognized as an important step in tumour pathogenesis that is related to invasion and metastatic spread and which consequently results in poor clinical outcome. In this study, we have examined the role of tumour stroma-activated fibroblasts and macrophage infiltration in the development of the angiogenic and metastatic phenotype in non-small-cell lung cancer (NSCLC). A total of 141 cases of early stage I-II NSCLC treated with surgery alone were analysed. The JC-70 (anti-CD31) MAb was used for the assessment of vascular grade. The P-GF.44C MAb was used to assess thymidine phosphorylase (TP) reactivity in cancer cells, stromal fibroblasts and macrophages. Cancer cell TP overexpression related to high vascular grade and to advanced T stage (P = 0.0004 and P = 0.02). Expression of TP in stromal fibroblasts also correlated with high angiogenesis (P = 0.01), but was independent of cancer cell expression. Fibroblast TP overexpression was related to abundant stroma (P = 0.003), suggesting that TP may be a marker of active stroma. Moreover, intense macrophage infiltration was associated with fibroblast TP reactivity, regardless of the amount of stroma, suggesting that macrophages may be a major contributor to TP expression in stroma. Survival analysis showed that cancer cell TP overexpression was related to poor prognosis (P = 0.005). Although stroma TP is related to angiogenesis, in the low vascular grade group it defined a group of patients with better prognosis (P = 0.02). It may be that fibroblast TP reactivity is an indirect marker of tumour infiltration by functional macrophages, which have an antitumour effect. We conclude that stromal macrophage and fibroblast TP reactivity may have an important role in non-small-cell lung cancer behaviour. Understanding the role of stromal fibroblasts and inflammatory cells and their interaction with oncoprotein expression is essential for the elucidation of lung cancer pathogenesis.

Concurrent conventionally factionated radiotherapy and weekly docetaxel in the treatment of stage IIIb non-small-cell lung carcinoma.

Docetaxel has shown remarkable radiosensitizing in vitro properties. In a previous phase I/II dose escalation study in non-small-cell lung cancer (NSCLC) we observed a high response rate after concomitant boost radiotherapy and weekly docetaxel. The maximum tolerated dose was 30 mg m(-2) week(-1). In the present phase II study we evaluated whether weekly docetaxel and conventionally fractionated radiotherapy could be better tolerated and equally effective in the treatment of locally advanced NSCLC. Thirty-five patients with T3, T4/N2, T3/M0-staged disease were recruited. Docetaxel (30 mg m(-2)) was given as a 30 min infusion once a week. Asthenia and radiation-induced oesophagitis were the main side-effects of the regimen enforcing 2-week treatment delay in 6/35 (17%) patients and minor delay (3-7 days) in another 11/35 (31%) patients. Neutrophil, platelet and haemoglobin toxicity was minimal, but pronounced lymphocytopenia was observed. Complete response (CR) of the chest disease was observed in 12/35 (34%) patients and partial response in 16/35 (46%). Although not statistically significant (P=0.19), a higher CR rate (8/18; 44%) was observed in patients who accomplished their therapy within the scheduled treatment time (44-47 days) as compared to patients that interrupted their treatment for several days due to treatment-related toxicity (CR 4/17; 23%). The overall survival and the local progression-free survival at 1 year was 48% and 60% respectively. We conclude that docetaxel combination with radiotherapy is a promising approach for the management of locally advanced NSCLC that results in high CR rate. Further trials with docetaxel-based radiochemotherapy should integrate accelerated radiotherapy together with cytoprotection.