Intense therapy in patients with locally advanced esophageal cancer beyond hope for surgical cure: a prospective, multicenter phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 76/02).

BACKGROUND: There is no standard treatment for patients with locally advanced esophageal carcinoma without systemic metastasis in whom surgery is no longer considered a reasonable option. PATIENTS AND METHODS: Patients with cervical esophageal tumors, locally very advanced stage (T4 and/or M1a) or locally advanced (T3 and/or N+) with comorbidities were included. THERAPY: 2 cycles of induction chemotherapy (cisplatin and docetaxel, both 75 mg/m(2) 3-weekly) followed by chemoradiation therapy (CRT) comprising a total radiation dose of 59.4 Gy together with docetaxel 15 mg/m(2) and cisplatin 25 mg/m(2) (5 weekly doses). Primary endpoint: Histologically proven freedom from local failure 6 months after CRT completion. RESULTS: 21 patients were included: 12 had locally very advanced tumors, 3 had cervical esophagus tumors, and 6 were medically unfit for surgery. 18 patients completed therapy per protocol. Grade 3/4 toxicities during CRT were thrombopenia (10%) and dysphagia (15%). 1 patient died due to herpes simplex infection. The primary endpoint was achieved by 4 patients, 6 were alive after median follow-up of 34 months, and median survival was 16 months. Most patients experienced lasting improvement of dysphagia following induction chemotherapy. CONCLUSIONS: This regimen is feasible, showed clinically meaningful, long-lasting improvements in quality of life and resulted in long-term survival in 29% of the patients.

Comparison of neoadjuvant cisplatin-based chemotherapy versus radiochemotherapy followed by resection for stage III (N2) NSCLC.

OBJECTIVE: Comparison of prospectively treated patients with neoadjuvant cisplatin-based chemotherapy vs radiochemotherapy followed by resection for mediastinoscopically proven stage III N2 non-small cell lung cancer with respect to postoperative morbidity, pathological nodal downstaging, overall and disease-free survival, and site of recurrence. METHODS: Eighty-two patients were enrolled between January 1994 to June 2003, 36 had cisplatin and doxetacel-based chemotherapy (group I) and 46 cisplatin-based radiochemotherapy up to 44 Gy (group II), either as sequential (25 patients) or concomitant (21 patients) treatment. All patients had evaluation of absence of distant metastases by bone scintigraphy, thoracoabdominal CT scan or PET scan, and brain MRI, and all underwent pre-induction mediastinoscopy, resection and mediastinal lymph node dissection by the same surgeon. RESULTS: Group I and II comprised T1/2 tumors in 47 and 28%, T3 tumors in 45 and 41%, and T4 tumors in 8 and 31% of the patients, respectively (P=0.03). There was a similar distribution of the extent of resection (lobectomy, sleeve lobectomy, left and right pneumonectomy) in both groups (P=0.9). Group I and II revealed a postoperative 90-d mortality of 3 and 4% (P=0.6), a R0-resection rate of 92 and 94% (P=0.9), and a pathological mediastinal downstaging in 61 and 78% of the patients (P<0.01), respectively. 5y-overall survival and disease-free survival of all patients were 40 and 36%, respectively, without significant difference between T1-3 and T4 tumors. There was no significant difference in overall survival rate in either induction regimens, however, radiochemotherapy was associated with a longer disease-free survival than chemotherapy (P=0.04). There was no significant difference between concurrent vs sequential radiochemotherapy with respect to postoperative morbidity, resectability, pathological nodal downstaging, survival and disease-free survival. CONCLUSIONS: Neoadjuvant cisplatin-based radiochemotherapy was associated with a similar postoperative mortality, an increased pathological nodal downstaging and a better disease-free survival as compared to cisplatin doxetacel-based chemotherapy in patients with stage III (N2) NSCLC although a higher number of T4 tumors were admitted to radiochemotherapy.

Endovascular brachytherapy after percutaneous transluminal angioplasty of recurrent femoropopliteal obstructions.

PURPOSE: To test the preventive effect of endovascular brachytherapy (EVBT) on restenosis following secondary angioplasty in patients with presumed neointimal restenosis in the femoropopliteal segment. METHODS: From March 1997 through May 2000, 100 patients (58 men; mean age 70 years, range 45-87) with postangioplasty femoropopliteal segment restenoses were enrolled and randomized to treatment with repeat angioplasty and EVBT (n=51) or to angioplasty alone (n=49) as control. The groups were similar with regard to demographics and lesion characteristics. High-dose-rate EVBT was performed with (192)Ir irradiation without a centering device (12 Gy for a reference vessel radius of 3 mm and a 2-mm reference depth). Primary endpoint in the 1-year follow-up was recurrent obstruction >50% documented by duplex ultrasound; the secondary endpoint was clinical improvement. RESULTS: Only 44 (86%) of 51 patients received adequate EVBT due to technical failure, so the 7 failures were included with the controls in the per-protocol adherence analysis. At 1 year, the patients receiving EVBT had a restenosis rate of 23% (10/44), which differed significantly (p<0.028) from the 42% (23/56) rate in controls. Clinical results tended to be better with EVBT, but differences did not achieve statistical significance. CONCLUSIONS: EVBT without a centering device reduced restenosis significantly in patients with recurrent stenosis after angioplasty, which confirms previous results in primary long-segment femoropopliteal obstructions.

Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial.

PURPOSE: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS: Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.

Endovascular brachytherapy for prevention of recurrent renal in-stent restenosis.

PURPOSE: To examine the ability of endovascular brachytherapy to prevent recurrent in-stent restenosis in patients at high risk for this complication. METHODS: Thirteen renal stent patients (8 women; mean age 66 +/- 8 years) with an initial (n=9) or recurrent (n=4) in-stent restenosis underwent redilation followed by high-dose-rate brachytherapy (12 Gy of gamma radiation delivered to the target site 5 mm from an iridium-192 source axis). RESULTS: The procedure was technically successful in 11 (85%) patients; in the other 2, the renal artery could not be accessed with the large sheaths required for brachytherapy. One patient with no clinical suspicion of restenosis died of an unrelated cause during the 1-year follow-up. Eight (80%) of 10 patients alive at 1 year had no in-stent restenosis apparent on duplex sonography or angiography. One of the postradiation recurrent restenoses was redilated, but the other patient was treated conservatively. CONCLUSIONS; Renal angioplasty followed by brachytherapy seems to be a feasible and efficient method to prevent recurrent in-stent restenosis in renal arteries at increased risk.

Intensive chemotherapy with whole blood stem-cell support and concurrent chest radiotherapy in small cell lung cancer: a phase I/II trial.

Intensive chemotherapy combined with chest radiation may ameliorate survival in small cell lung cancer (SCLC). In a prospective study, we treated 18 patients with limited SCLC with an intensive sequential single agent (ifosfamide, carboplatin, etoposide and paclitaxel, (ICE-T)) chemotherapy with the support of unprocessed stem-cell enriched whole blood and G-CSF and concomitant bi-fractionated chest radiotherapy (60 Gy). The treatment was delivered in a short time of 10 weeks. The results were compared with an historical patient group treated with six cycles of standard chemotherapy of etoposide and cisplatin and concomitant chest radiotherapy. After a 3-year median follow up, the 2-year progression free (PFS) and overall survival (OS) are 54 and 63% in the ICE-T group, respectively. In the control group, median PFS and OS were 13 and 17 months and the 2-year PFS and OS were 32% (P=0.20) and 47% (P=0.25), respectively. This short and intensive chemo-radiotherapy regimen is well tolerated and induces promising survival results. The use of stem cell enriched whole blood should be investigated in larger randomized studies.