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Background and Purpose:  Transurethral resection of bladder tumor (TUR-BT) and radiochemotherapy with cisplatin achieve high rates of bladder preservation and survival figures identical to radical cystectomy in muscle-invasive bladder cancers. The authors have investigated the potential use of paclitaxel in a radiochemotherapy protocol for patients with inoperable bladder carcinomas and mainly contraindications to cisplatin. Patients and Methods:  Between October 1997 to August 2004, 42 patients (median age 71 years) suffering from muscle-invasive (n = 32) or recurrent (n = 10) bladder cancers were treated with a paclitaxel-containing radiochemotherapy (paclitaxel 25–35 mg/m2 twice weekly) after TUR-BT (R0/1/2/x in n = 18/4/14/3) or cystectomy with residual tumor (n = 3). Five patients received additional cisplatin. Radiation treatment was administered to a total dose of 45–60 Gy. Results:  76.2% completed the planned regimen. Adaptations of treatment were mainly required due to diarrhea. Grade 3/4 toxicities occurred in 15/1 patients. Severe renal toxicities did not occur. 28 patients underwent restaging TUR-BT 6 weeks after radiochemotherapy (complete remission/partial remission/progressive disease: n = 24/3/1). Three patients developed a local recurrence and four distant metastases. Seven patients died from tumor, six of other reasons. Conclusion:  Radiochemotherapy with paclitaxel was feasible and this bladder approach needs further investigation to evaluate whether paclitaxel could become a substitute for cisplatin. [ABSTRACT FROM AUTHOR]

Background. Simultaneous radiochemotherapy (RCT) is the treatment of choice for locally advanced headand neck cancers. In order to evaluate the toxicity and the survival rates, we investigated the use of a veryaggressive combination protocol that included cisplatinum and paclitaxel combined with hyperfractionatedacceleratedradiotherapy. The final results of the phase II study are listed below.Methods. For the phase II trial 32 patients (29 male, 3 female) with histologically diagnosed locallyadvanced non-metastatic squamous cell carcinoma of the head and neck in stage III/IV were treated from 1999to 2003. Radiotherapy was administered as hyperfractionated-accelerated to a total dose of 70.6 Gy. Thechemotherapy regime included administering cisplatinum on d 1-5 and on d 29-33 at doses of 20 mg/m2 andduring the entire course of treatment paclitaxel was administered twice a week at doses of 25 mg/m2.Results. The 5-yr overall and disease-free survival rates were 48% and 43%. Twenty-two (69%) patientsreached a clinically complete response and 8 (25%) a partial response (for two of the patients the response rateis not known). Two (6%) patients died during the treatment. Seven (22%) patients developed local recurrencesand six of these patients have in the meantime died. With regards to the four (12%) patients who developeddistant metastases, three of them have in the meantime died and two (6%) patients have died as a result of secondarymalignancies.Seven out of 25 (28%) patients developed grade 3 erythema and 22 out of 31 (71%) patients developedgrade 3 mucositis. No cases of grade 4 mucositis were observed; however, one patient out of 25 (4%) was classifiedwith grade 4 dermatitis. One out of 24 (4%) patients developed grade 2 liver toxicity and 1 out of 22patients (5%) developed grade 3 thrombopenia. Seven out of 25 patients (28%) developed a grade 3 leukopenia,and 2 out of 25 patients (8%) experienced a grade 4 eutropenic infection. Dysphagia was a significant latetoxicity. Out of 24 patients, 4 (17%) developed a grade 3 dysphagia and 1 (4%) patient developed a grade 3xerostomia. An osteoradionecrosis was seen in 2 out of 24 (8%) patients.Conclusion. This very aggressive radiochemotherapy protocol yielded excellent response and overall survivalrates; however it is associated with a very high rate of acute toxicity. Therefore, in such cases whereacute toxicity resulted, extensive supportive care is required. [ABSTRACT FROM AUTHOR]

Background: Simultaneous radiochemotherapy (sRCT) is the treatment of first choice in locally advanced head and neck cancers. We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. Patients and Methods: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m 2 on days 1?5 and 29?33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m 2 twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 ± 61 cm 3. The mean follow-up was 30 months (range 4?39 months). Results: One early death (peritonitis and sepsis at day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m 2 paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m 2 twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30 of neutropenic infection. In one patient, a grade 2 nephrotoxicity appeared requiring cessation of cisplatin chemotherapy. 18/23 patients (78%) required blood transfusion (1?3 units) and 16/23 (70%) i.v. antibiotics. 14 patients (61%) achieved a complete and nine (39%) a partial remission, yielding an overall response rate of 100%. In summary, six patients died of local tumor progression (n = 2), distant metastases (n = 2), or therapy-related complications (n = 2) during follow-up. The 3-year overall survival was 71%. Tumor volume was not a risk factor for failure in this protocol (mean tumor volume in relapse-free vs. progressive patients 71 ± 65 cm 3 vs. 64 ± 38 cm 3). All patients have, so far, developed only slight late effects (fibrosis, lymphedema) with no grade 3?4 late sequelae. Conclusions: This very aggressive sRCT protocol yielded excellent response and survival figures but was associated with a very high rate of acute toxicity (8% therapy-related deaths). A maximal supportive treatment is therefore required. [ABSTRACT FROM AUTHOR]

Background: The prognostic impact of tumor volume and hypoxia is well established. We have investigated a possible prognostic impact of the hypoxic tumor volume which can be calculated as the product of tumor volume and hypoxia. Patients and Methods:125 patients with squamous cell cancer of the head and neck were investigated. All had locoregionally confined disease. The total tumor volume was calculated from pretreatment CT scans as the sum of all visible macroscopic tumor lesions (e.g., primary tumor plus neck nodes), and all patients underwent measurement of tumor oxygenation by pO 2 histography. The hypoxic tumor volume was calculated as the product of the total tumor volume and the relative frequency of pO 2 readings < 5 mmHg. The nonhypoxic volume was the difference between total tumor volume and hypoxic volume. Results: The total tumor volume ranged from 2 to 283 cm3 (mean 47 ? 53 cm 3), the hypoxic volume from 0 to 199 cm3 (mean 18 ? 30 cm 3), and the nonhypoxic volume from 1 to 237 cm 3 (mean 29 ? 34 cm 3), and there was a strong correlation between the three parameters. 84 patients died and 41 survived in the observation period with a median survival of 12.5 months. Tumor volume and tumor oxygenation had a significant impact on survival. The tumor volume was significantly different in patients who had died as compared to surviving patients (mean 54 vs. 34 cm 3; p = 0.017). The hypoxic volume was also different (11 vs. 22 cm 3; p = 0.009), whereas the nonhypoxic volume was not significantly different (24 vs. 32 cm 3; p = 0.2). If the impact of large versus small tumor volumes (total volume, hypoxic volume, and nonhypoxic volume, subdivison according to each median) on survival was analyzed, a significant impact of total tumor volume (median survival 298 vs. 485 days; p = 0.03) and a marginal impact of the hypoxic volume (342 vs. 404 days; p = 0.08), but no impact of the nonhypoxic volume were found (383 vs. 374 days; p = 0.6). In a multivariate Cox regression model, the hypoxic tumor volume was a strong and independent prognostic factor for survival (p = 0.001) and more important than the total tumor volume (p = 0.02) whereas the nonhypoxic volume had no impact on prognosis (p = 0.33). Conclusion: The total tumor volume is a major prognostic factor, but its impact mainly results from the hypoxic volume and can be explained by the strong correlation between total tumor volume and hypoxic volume. The nonhypoxic volume had no impact on survival. As a consequence, methods to measure and localize the hypoxic volume should be further developed. [ABSTRACT FROM AUTHOR]

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