Locoregional Tumor Progression Research Articles

Treatment of genitourinary carcinoma in dogs using nonsteroidal anti-inflammatory drugs, mitoxantrone, and radiation therapy: A retrospective study.

BackgroundLocoregional tumor control and prolonged survival for dogs with genitourinary carcinoma (CGUC) reportedly are achievable using treatment with radiotherapy (RT) with or without adjunctive chemotherapy and nonsteroidal anti‐inflammatory drugs (NSAIDs).ObjectivesTo characterize event‐free and overall survival after treatment of CGUC using NSAIDs, mitoxantrone (MTX), and a standardized RT protocol (57 Gy in 20 fractions).AnimalsFifty‐one client‐owned dogs treated between 2008 and 2017.MethodsDogs were retrospectively categorized into treatment groups: (a) first‐line concurrent chemoradiotherapy (≥1 dose of MTX started within 1 month of RT); (b) first‐line chemotherapy (MTX administered for >1 month before RT without tumor progression); (c) RT as a salvage procedure (MTX, surgery or both with subsequent locoregional tumor progression before RT). Treatment‐induced toxicoses, event‐free survival (EFS), and overall survival times (OSTs) were recorded. The influence of demographics, staging, and treatment‐related factors on survival was assessed using Cox proportional hazards modeling.ResultsMedian EFS and OST for all dogs were 260 and 510 days with no significant differences among groups 1 (n = 39), 2 (n = 4), and 3 (n = 8). Both EFS and OST were shorter in dogs with moderate to severe clinical signs (P < .001 and P < .001, respectively); OST was shorter in dogs with prostatic involvement (P = .02). Permanent urinary incontinence developed in 16 dogs (31%) at a median of 70 days postirradiation; other toxicoses were mild and self‐limiting.Conclusions and Clinical ImportanceMild clinical signs and lack of prostate involvement were associated with favorable prognosis for survival. Client education regarding the risk of urinary incontinence is warranted.

Locoregional progression in patients with pancreatic ductal adenocarcinoma

Introduction: It is well recognized that pancreatic ductal adenocarcinoma (PDAC) is associated with very poor prognosis, early locoregional invasion and distant metastases. One reason for this is the proliferation of tumor growth through perineural spaces. Methods: To evaluate the efficacy of intraoperative radiation therapy (IORT) for the extrapancreatic perineural invasion (EPPI) in the development of locoregional recurrence in patients with PDAC. Results: In 14.5% (22/152) the tumor was pT1-2, pN0, EPPI 0, R0. R1 detected in 32.1% (49/152). EPPI was detected in 36.8% of cases (56/152). Metastases in regional lymph nodes was found in 62.5% (95/152) of cases. In the study of autopsy basic morphological parameters speakers include locoregional tumor progression and / or a distant progression. Locoregional recurrence was found in 85% of cases (29/34), which is manifested by the presence of perineural invasion. The mean time from surgery until locoregional recurrence without EPPI - 14 months, with the presence of EPPI - 9 months. Conclusion: Thus, the absence of regional lymph nodes and/or with positive surgical margin does not preclude the development of locoregional recurrence in patients with PDAC. This is what necessitates a combined approach to the treatment of these patients, including surgery, supplemented by conducting IORT that effectively influences on tissues and reduces the number of local recurrence.

Morphological background of intraoperative radiation therapy appliance to prevent locoregional progression in patients with pancreatic ductal adenocarcinoma

Background. It is well recognized that pancreatic ductal adenocarcinoma (PDAC) is associated with very poor prognosis, early locoregional invasion and distant metastases. One reason for this is the proliferation of tumor growth through perineural spaces. Aim. To evaluate the efficacy of intraoperative radiation therapy (IORT) for the extrapancreatic perineural invasion (EPPI) in the development of locoregional recurrence in patients with PDAC. Results. In 14.5% (22/152) the tumor was pT1–2, pN0, extraPn 0, R0. R1 detected in 32.1% (49/152). ExtraPn was detected in 36.8% of cases (56/152). Metastases in regional lymph nodes was found in 62.5% (95/152) of cases. In the study of autopsy basic morphological parameters speakers include locoregional tumor progression and / or a distant progression. Locoregional recurrence was found in 85% of cases (29/34), which is manifested by the presence of perineural invasion. The mean time from surgery until locoregional recurrence without extraPn –14 months, with the presence of extraPn – 9 months. Conclusion. Thus, the absence of regional lymph nodes and/or with positive surgical margin does not preclude the development of locoregional recurrence in patients with PDAC. This is what necessitates a combined approach to the treatment of these patients, including surgery, supplemented by conducting IORT that effectively influences on tissues and reduces the number of local recurrence.

Extrapulmonary Small Cell Carcinoma - a Case Series of Oropharyngeal and Esophageal Primary Sites Treated with Chemo-Radiotherapy.

The optimal sequence and extent of multimodality therapy remains to be defined for extrapulmonary small cell carcinoma because of its rarity. The purpose of our study was to assess the response to neoadjuvant chemotherapy followed by chemoradiation/radiation in patients with extrapulmonary small cell carcinoma. Four consecutively diagnosed patients were included in this study. The primary tumor site was oropharynx in three patients and esophagus in one. The patients with the limited disease were treated with chemotherapy followed by concurrent chemoradiation (n=2) or radiotherapy (n=1). The patient with the extensive disease with the primary site in vallecula was treated with chemotherapy and palliative radiotherapy to the metastatic site. The median follow-up was 22.5 months (range, 8-24 months). Three patients with the limited disease (base of tongue, n=2; esophagus, n=1) were in complete remission. The patient with the extensive disease died of loco-regional tumor progression at 8 months from the time of diagnosis. The combination of chemotherapy and radiotherapy is the preferred therapeutic approach for patients with extrapulmonary small cell carcinoma. Induction chemotherapy followed by concurrent chemoradiation or radiation provides a good loco-regional control in patients with limited disease.

Chimioradiothérapie de rattrapage à visée curative de rechutes pelviennes isolées de cancers du col utérin

PurposeEvaluation of the results of salvage radiation therapy with curative intent in the treatment of recurrent cervical carcinoma. Patients and methodsFourteen patients with a recurrence of a cervical cancer were treated in our department between 1982 and 2009. Five patients had a pelvic relapse, four a vaginal relapse and five a pelvic lymph node relapse. Four patients had first a surgical resection of the relapse, which was incomplete in two patients. All patients had pelvic radiotherapy with a median dose of 55Gy in conventional fractionation. Concurrent chemotherapy was administered to 12 patients. A vaginal brachytherapy with a median dose of 20Gy was performed in addition in 3 patients. The median follow-up was 39months. ResultsSafety of radiation therapy was correct with 29% of grade 3 acute or intestinal toxicity. Tumor control was observed in 10 patients (71%). Four patients presented a locoregional tumor progression. At the time of analysis, three patients had died from their cancer. From the date of relapse, the rate of overall survival at 2 and 5year was respectively 84% and 74%. Three patients (21%) had severe late effects. ConclusionIn our experience, chemoradiotherapy can achieve a high rate of remission in patients with isolated pelvic recurrence of cervical cancer. This treatment is feasible only if the patient had not received radiation therapy before or if the relapse is out of the previously irradiated volume.

Outcome of platinum-based chemotherapy for non-small-cell lung cancer patients with pleural dissemination detected during surgery

Pleural dissemination detected by computed tomography (CT) is considered to be unfavorable for patients with non-small-cell lung cancer (NSCLC). However, the prognosis of NSCLC patients who are diagnosed with pleural dissemination at the time of surgery has yet to be adequately elucidated. To assess the outcomes of platinum-based chemotherapy in NSCLC patients in whom pleural dissemination was detected during exploratory thoracotomy with or without a videoscope, the clinical records of NSCLC patients who were admitted to Shizuoka Cancer Center between September, 2002 and April, 2009 were reviewed. A total of 19 patients were included in this study, 12 males and 7 females, with a median age of 65 years. All patients were diagnosed with adenocarcinoma and 6 were epidermal growth factor receptor (EGFR) gene mutation-positive. The median number of treatment cycles of first-line platinum-based chemotherapy was 4 (range, 1-6 cycles) and the objective response rate was 21% [95% confidence interval (CI): 8.5-43]. The median progression-free and overall survival were 10.4 (95% CI: 6.3-18.4) and 50.5 months (95% CI: 32.5-98.0), respectively. Of the 18 patients with reported disease progression, 9 (50%) developed locoregional tumor progression. In conclusion, NSCLC patients in whom pleural dissemination is detected during surgery tend to have a favorable prognosis for survival. Systemic chemotherapy and additional local treatment may improve their clinical outcomes.

Radiotherapy combined with hyperthermia for primary malignant melanomas of the esophagus

Primary malignant melanoma of the esophagus (PMME) forms about 0.1% of all primary esophageal cancers. Treatment options are very limited for patients unfit for surgery. This is the first report describing the results of external radiotherapy combined with regional hyperthermia for two inoperable PMME patients. Two patients with a T2-3N0M0 PMME were considered unfit for surgery based on age and general condition. External radiotherapy of a total dose of 35 Gy was given in a scheme of seven times 5 Gy, two times per week, and once weekly combined with external and intraluminal hyperthermia (aim 43°C). Toxicity was mild and both patients completed treatment according to protocol. Adequate temperatures at the intraluminal border of the tumor were achieved. In both patients, a complete remission was achieved with complete relief of obstructive symptoms and without signs of locoregional tumor progression until the end of follow-up at 11 and 15 months. External radiation combined with regional hyperthermia could be a good alternative to resection in patients unfit for surgery with a malignant melanoma of the esophagus.

Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. With a median follow-up of 34 months +/- 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

How to improve loco-regional control in stages IIIa–b NSCLC?: Results of a three-armed randomized trial from the Swedish Lung Cancer Study Group

Background A combination of chemotherapy and radiotherapy is the treatment base for locally advanced non-small cell lung cancer (NSCLC). However, both loco-regional and distant failure is frequent. Attempts to improve the loco-regional control were made in three separate phase II studies in Swedish University Hospitals, where accelerated radiotherapy or concurrent daily or weekly chemotherapy with conventional radiotherapy were tested. Comparatively good results from these studies lead to this national randomized phase II study, the RAKET-study, where the different concepts were investigated on a wider basis for further phase III studies. Methods Inoperable stage III non-small cell lung cancer patients in good performance status (PS < 2) were equally randomized to either of three arms in eight institutions. All arms started with two cycles of induction chemotherapy: paclitaxel 200 mg/m 2 and carboplatin AUC6. Arm A: a third identical cycle was given concomitant with start of accelerated radiotherapy, 1.7 Gy BID to 64.6 Gy in 4.5 weeks. Arm B consisted of daily concomitant paclitaxel 12 mg/m 2 with conventionally fractionated radiotherapy: 2 Gy to 60 Gy in 6 weeks. Arm C: weekly concomitant paclitaxel 60 mg/m 2 and identical radiotherapy to 60 Gy. Primary endpoint: TTP. Secondary: OS, toxicity, QL and relapse pattern. Results Between June 2002 and May 2005 152 patients were randomized and of them 151 were evaluable: 78 men and 73 women, median age 62 years (43–78), 55% had performance status 0 and 45% PS 1. Thirty-four percent had stage IIIa and 66% IIIb. Histology: adenocarcinoma 48%, squamous cell carcinoma 32% and 20% non-small cell carcinoma. The three arms were well balanced. Toxicity was manageable with 12% grades 3–4 esophagitis, 1% grades 3–4 pneumonitis and there was no clear difference between the arms. The QL data did not differ either. Median time to progression was 9.8 (8.3–12.7) months (8.8, 10.3 and 9.3 months for arms A, B and C, respectively). Median survival was 17.8 (14.4–23.7) months (17.7, 17.7 and 20.6 months for A, B and C, respectively). The 1-, 3- and 5-year overall survival was 63, 31 and 24%. Sixty-nine percent of the patients relapsed with distant metastases initially and 31% had loco-regional tumor progression, without significant differences between treatment arms. Thirty-four percent developed brain metastases. Conclusions Treatment results are quite equal by intensifying the loco-regional treatment either by accelerated fractionated radiotherapy or daily or weekly concomitant chemo-radiotherapy both in terms of survival, toxicity and quality of life. The optimal treatment schedule for patients with locally advanced NSCLC is still to be decided and investigated in future clinical studies. Relapse pattern with distant metastases and especially brain metastases is a great problem and need further research for better therapy options and higher cure rate for this patient group.

Squamous cell carcinoma of the maxillary sinus: A Tata Memorial Hospital experience

The optimal treatment of maxillary sinus carcinoma remains to be defined and there is a paucity of Indian studies on the subject. To present experience of management of squamous cell carcinoma of the maxillary sinus treated with curative intent at a single institution. Retrospective study of patients with squamous cell carcinoma of the maxillary sinus who presented between 1994 to 1999. The records of 73 patients with squamous cell carcinoma of the maxillary sinus were analyzed. Sixty-two patients were evaluable. Forty patients (65%) were treated with surgery followed by postoperative radiotherapy, five patients (8%) were treated with radiotherapy alone, five patients (8%) were treated with surgery alone; 12 patients (19%) received chemotherapy. Statistical analysis was done using Kaplan-Meier method. The majority of patients presented with locally advanced disease (52, 84%); nodal involvement was observed in five patients (8%). The most common site of recurrence was at the primary site, which was observed in 28 patients (45%) and regional failures occurred in 10 (16%). The 3 and 5-year overall survival was 38% and 35% and the disease free survival was 29% and 26% respectively. The 5-year overall survival after surgery and postoperative radiotherapy was 42%. The majority of patients present with advanced disease resulting in poor outcomes to conventional treatment modalities. Locoregional tumor progression remains a significant pattern of failure. New approaches such as neoadjuvant or concomitant chemoradiotherapy with aggressive surgery need to be considered and evaluated in prospective studies.

Small cell carcinoma of bladder: A single-center prospective study of 25 cases treated in analogy to small cell lung cancer

To evaluate the feasibility and efficacy of a therapeutic algorithm for the management of small cell carcinoma of the bladder derived from the treatment of small cell lung cancer. During a 10-year period, 25 patients (23 men and 2 women; median age 64 years, with 8 [32%] older than 75 years) with small cell carcinoma of the bladder were defined as having limited disease (LD) or extensive disease (ED) in analogy to the classification of small cell lung cancer. Patients with LD were eligible for chemotherapy and sequential radiotherapy. Patients unfit for chemotherapy were offered complete transurethral resection and radiotherapy or cystectomy for large symptomatic tumors. Patients with ED were offered palliative chemotherapy. Of the 25 patients, 17 (68%) had LD and 8 (32%) ED. Without regard to stage, the median survival of those receiving chemotherapy was 15 months versus 4 months for those who did not. The median survival for those with LD was 12 months versus 5 months for those with ED. Nine patients (52.9%) with LD could not undergo chemoradiotherapy because of comorbidity and reduced performance (n = 7), progression (n = 1), or drug-related death (n = 1). Five of those patients underwent TUR and radiotherapy and two cystectomy. The prognosis of small cell carcinoma of the bladder is poor. This treatment algorithm offers bladder sparing for most patients, with few long-term remissions in patients with small, confined tumors. None of the patients died of locoregional tumor progression, supporting that cystectomy is not the treatment of choice for those with LD. With a significant proportion of elderly patients with comorbidities, chemoradiotherapy was not feasible in more than one half of the patients with LD.

XPC, XPD/ERCC2, UMPS, CYP1b1 and XRCC5, single nucleotide polymorphisms (SNPs) in head and neck cancer

5588 Background: SNPs located in the exonic region of XPC, XPD/ERCC2, UMPS, CYP1b1 and in the 3'UTR region of XRCC5 are involved in nucleotide excision repair and drug metabolism. We analyzed these SNPs and correlated the results with time to relapse (TTR), survival and response in head and neck cancer patients (p). Methods: PCR allelic discrimination (ABI Prism 7700 sequencer detector) was used to examine SNPs in DNA from tumor tissue obtained from 190 head and neck cancer p accrued from June 1985 to July 2002. Results: Characteristics of the initial 190 p: median age, 69 years; 170 PS 0–1, 20 PS >2; stage: I-39, II-24, III-32, IV-95. The most frequent tumor location was larynx (83p). Locoregional tumor progression was observed in 62% of p. 80% of p received concomitant chemoradiotherapy. Frequencies of genotypes: XPC: 82 TT, 105 TG; XPD/ERCC2: 70 AA, 89 AC, 31 CC; UMPS: 142 GG, 48 GC; CYP1b1: 50 CC, 106 CG, 34 GG; XCRR5: 146 AA, 39 AG. A correlation was found between XPD/ERCC2 and XRCC5 (P<0.04). No other correlation between genotypes was observed. TTR for all p was 16.5 months (m) (95%CI, 9.6–23). TTR was 15 m for UMPS GG vs 10 m for UMPS GC at pharynx (P=0.05), 26 m for CYP1b1 CC vs 50 m for CYP1b1 CG+GG at larynx (P=0.008), and 8.3 m for CYP1b1 CC vs 14.6 m for CYP1b1 CG+GG at pharynx (P=0.008). Overall median survival was 30.3 m but has not been reached for p with different genotypes. Response rate in p receiving concommitant chemoradiotherapy was 86% for p with UMPS CC vs 14% for p with UMPS CG (P=0.03), and 14% for p with CYP1b1 CC vs 86% for p with CYP1b1 CG+GG (P=0.04). Conclusions: CYP 1b1 and UMPS are expressed mainly in larynx and pharynx tumors and may be predictive markers in head and neck cancer. No significant financial relationships to disclose.

XPC, XPD/ERCC2, UMPS, CYP1b1 and XRCC5, single nucleotide polymorphisms (SNPs) in head and neck cancer

5588 Background: SNPs located in the exonic region of XPC, XPD/ERCC2, UMPS, CYP1b1 and in the 3'UTR region of XRCC5 are involved in nucleotide excision repair and drug metabolism. We analyzed these SNPs and correlated the results with time to relapse (TTR), survival and response in head and neck cancer patients (p). Methods: PCR allelic discrimination (ABI Prism 7700 sequencer detector) was used to examine SNPs in DNA from tumor tissue obtained from 190 head and neck cancer p accrued from June 1985 to July 2002. Results: Characteristics of the initial 190 p: median age, 69 years; 170 PS 0–1, 20 PS >2; stage: I-39, II-24, III-32, IV-95. The most frequent tumor location was larynx (83p). Locoregional tumor progression was observed in 62% of p. 80% of p received concomitant chemoradiotherapy. Frequencies of genotypes: XPC: 82 TT, 105 TG; XPD/ERCC2: 70 AA, 89 AC, 31 CC; UMPS: 142 GG, 48 GC; CYP1b1: 50 CC, 106 CG, 34 GG; XCRR5: 146 AA, 39 AG. A correlation was found between XPD/ERCC2 and XRCC5 (P<0.04). No other correlation between genotypes was observed. TTR for all p was 16.5 months (m) (95%CI, 9.6–23). TTR was 15 m for UMPS GG vs 10 m for UMPS GC at pharynx (P=0.05), 26 m for CYP1b1 CC vs 50 m for CYP1b1 CG+GG at larynx (P=0.008), and 8.3 m for CYP1b1 CC vs 14.6 m for CYP1b1 CG+GG at pharynx (P=0.008). Overall median survival was 30.3 m but has not been reached for p with different genotypes. Response rate in p receiving concommitant chemoradiotherapy was 86% for p with UMPS CC vs 14% for p with UMPS CG (P=0.03), and 14% for p with CYP1b1 CC vs 86% for p with CYP1b1 CG+GG (P=0.04). Conclusions: CYP 1b1 and UMPS are expressed mainly in larynx and pharynx tumors and may be predictive markers in head and neck cancer. No significant financial relationships to disclose.

Carcinoma of paranasal sinuses: long-term outcomes with radiotherapy

Purpose To assess the clinical features, prognostic factors, results, and complications of treatment of carcinomas of the paranasal sinus. Methods and materials The records of 106 patients (72 men and 34 women) with paranasal sinus carcinoma treated with curative intent at Washington University between January 1960 and August 1998 were analyzed. Patient age ranged from 29 to 91 years (median, 64 years). Most tumors originated in the maxillary (76%) or ethmoid (18%) sinus. Most tumors were locally advanced at presentation. All patients underwent radiotherapy (RT), combined with surgery in 65%; 2% received chemotherapy. Results Follow-up ranged from 1.7 months to 24 years (median 5 years). The 5-year local tumor control, locoregional tumor control, disease-free survival (DFS), and overall survival rate was 58%, 39%, 33%, and 27%, respectively. A statistically significant improvement in DFS was noted with the addition of surgical resection to RT (35% vs. 29%, p = 0.05). Nodal status at presentation emerged as a statistically significant predictor for locoregional tumor control and DFS in multivariate analysis. Distant metastases occurred in 29% of patients. Conclusion This review of a large, single-institution experience of paranasal sinus carcinoma patients who underwent RT showed that locoregional tumor progression and recurrence remain predominant patterns of failure despite aggressive local treatment with combined surgery and RT. DFS improved slightly with combined modality treatment. The overall survival rates remained suboptimal, suggesting a need for more accurate determination of tumor extent, as well as more effective locoregional and systemic therapies.

Should patients with post-resection locoregional recurrence of lung cancer receive aggressive therapy?

The outcome of thirty-seven patients with a post-resection locoregional recurrence of non-small cell lung cancer treated with radiation therapy alone between 1979 and 1989 was compared to that of 759 patients with unresected non-small cell lung cancer also treated with standard radiation during the same period. Each patient's locoregional recurrence was staged using the current American Joint Committee on Cancer staging system. Comparison of pretreatment characteristics between the two groups, including age, sex, extent of weight loss, performance status, stage, and histologic subtype revealed fewer patients with > 5% weight loss (35 vs. 47%, p = 0.04) and more cases with squamous histology (54 vs. 28%, p = 0.01) among the patients with locoregional recurrences than those with newly diagnosed lesions. Over 80% of both groups had clinical stage III lesions. The median radiation doses were 56 and 59 Gy for recurrent and newly diagnosed cases ( p = NS). For the patients with locoregional recurrences, the median time from resection to recurrence was 13 months (range: 3–118 months), and the recurrences were predominantly nodal in 25 cases, chest wall/pleural in four and at the bronchial stump in eight. When measured from the date of documented recurrence, the median survival time and 2-year actuarial survival rate of the patients with recurrent lesions were 12 months and 22%, as compared to 12 months and 26% for the newly diagnosed patients ( p = NS). Freedom from documented locoregional tumor progression at 2 years was 30% for both groups. Patients with bronchial stump lesions had superior survival to those with nodal or chest wall recurrences, with a median survival time of 36 versus 9 months. A therapeutic approach to selected patients with post-resection locoregional recurrence of non-small cell lung cancer equally aggressive to that for newly diagnosed lung cancer patients is justified by these results, especially for patients with bronchial stump recurrences.

Ifosfamide in patients with recurrent non small cell lung cancer

Summary1Recurrent intrathoracic disease remains an important problem in patients with non-small cell lung cancer (NSCLC). Data in the literature support the general assumption that patients previously treated with irradiation and/or chemotherapy have a very poor survival rate. Between May 1983 and May 1984, we treated 21 patients (20 males, 1 female; median age: 58 years; median performance status: 70) with ifosfamide. All patients had locoregional tumor progression with 2 patients having additional bone metastases. Patients with liver metastases were excluded from our study. Tumor histology included squamous cell carcinoma (n = 18), adenocarcinoma (n = 2) and alveolar-cell carcinoma (n = 1). Pretreatment consisted of radiotherapy in all patients and additional chemotherapy in 5 patients. Ifosfamide was administered by continuous infusion over 4 days (median dose: 1.75 g/m2 B.S.A./24 h). Mesna was given in a dose of 200 mg every 4 h i.v. Generally treatment was well tolerated, with gastrointestinal toxicity usually grade 1 (WHO criteria). Regarding myelosuppressive toxicity, there was no grade 3 or 4 toxicity. In only 1 patient did we observe progressive disease, while in 17 patients we noticed stable disease. Median time to progression was 7.0 months. From these 17 patients 11 showed a significant clinical improvement. According to standard criteria there was PR in 2 and CR in 1 patient. From this study we conclude that ifosfamide in pretreated and recurrent NSCLC administered by continuous infusion is tolerable and apparently prolongs the median duration of response.