Post-radiation severe xerostomia relieved by pilocarpine: a prospective French cooperative study.

BACKGROUND AND PURPOSE: The aim of the study was: (1) to confirm the action of pilocarpine hydrochloride (Salagen) against xerostomia: (2) to correlate the response to dose/volume radiotherapy parameters. MATERIALS AND METHODS: From June 1995 to February 1996, 156 patients with severe radiation induced xerostomia received pilocarpine hydrochloride orally. IS mg per day with a 5 mg optional increase at S weeks up to a daily dose of 25 mg beyond 9 weeks. RESULTS: One hundred and forty five patients are fully evaluable. Treatment compliance was 75%. Thirty eight patients (26%) stopped treatment before week 12 for acute intolerance (sweating, nausea, vomiting) or no response. No severe complication occurred. Ninety ses en patients (67%) reported a significant relief of symptoms of xerostomia at 12 weeks. Within 12 weeks, the size of the subgroup ith normal food intake almost doubled (13-24 patients) while the size of the subgroup with (nearly) impossible solid food ingestion decreased by 38% (47 vs. 29 patients). The impact on quality of life was considered important or very important by 77% of the responders. CONCLUSIONS: No difference was found according to dose/volume radiotherapy parameters suggesting that oral pilocarpine hydrochloride: (1) acts primarily by stimulating minor salivary glands: (2) can be of benefit to patients suffering of severe xerostomia regardless of radiotherapy dose/volume parameters: (3) all responders are identified at 12 weeks.

Complications of postoperative radiation therapy after partial laryngectomy in supraglottic cancer: A long-term evaluation.

This retrospective study, based on a series of 90 patients with invasive squamous cell carcinoma of the supraglottis, was designed to document the functional outcome and complications after postoperative radiation therapy following partial laryngeal surgery. The surgical procedure was a standard supraglottic laryngectomy in 62 patients and a supracricoid partial laryngectomy in 28 patients. All of the patients had an unremarkable postoperative course and achieved locoregional control. The average dose delivered to the remaining larynx was 51.2 Gy (range 25-71 Gy). The average dose delivered to the neck was 50.6 Gy (range 22-70 Gy). The patients were treated at 180-cGy per fractions in a continuous course technique with a cobalt 60 beam. In 5 patients (5.5%) complications led to cessation of postoperative radiation therapy, and the total dose delivered to the remaining larynx and neck was less than 40 Gy. All patients were followed up for a minimum of 10 years or until death. The 5-, 10-, and 15-year actuarial survival estimates were 71. 5%, 44.3%, and 36.3%, respectively. The 5-, 10-, and 15-year actuarial severe complication estimates were all 11.2%. Overall, severe complications occurred in 15 patients. Severe complications led to death in 3 patients (3.3%), permanent gastrostomy in 3 (3.3%), and permanent tracheostomy in 1 (1.1%). A severe complication never resulted in completion of total laryngectomy. In univariate analysis, the mean dose delivered to the larynx was the only variable statistically related to the incidence of a severe complication. The mean dose delivered to the larynx was statistically higher (P = 0.014) in patients who had severe complications (60 Gy) than in patients who did not (50 Gy).

[Prognostic factors of infiltrating tumors of the bladder]. / Facteurs pronostiques des tumeurs infiltrantes de vessie.

In France, invasive bladder cancer is the more frequent urologic malignancy after prostate carcinoma. Treatment of bladder cancer is radical cystectomy. New therapeutic approaches such as chemoradiation combination for a conservative procedure, neoadjuvant or adjuvant chemotherapy are still developing. In this way, a rigorous selection of patients is needed. This selection is based on prognostic criteria that could be divided into four groups: i) the volume of the tumor including the tumor infiltration depth, the nodal status, the presence or not of hydronephrosis and the residual tumor mass after transuretral resection; ii) the histologic aspects of the tumor including histologic grading, the presence or not of an epidermoid metaplasia, of in situ carcinoma or of thrombi; iii) the expression of tumor markers (tissue polypeptide antigen, bladder tumor antigen); iv) the biologic aspects of the tumor as ploidy, cytogenetic abnormalities, expression of Ki67, expression of oncogenes or tumor suppressor genes, expression of tumor antigens or growth factor receptors. This paper reviews the prognostic value of the various parameters.

Serum tissue polypeptide antigen in bladder cancer as a tumor marker: a prospective study.

PURPOSE: Tissue polypeptide antigen (TPA) is a differentiation and proliferation tissue marker of epithelia. Increased serum levels were found in some patients with invasive bladder cancer. We present the results of a prospective study that evaluated the role of serum TPA (S-TPA) in bladder carcinoma. PATIENTS AND METHODS: The series included 167 patients treated for invasive bladder cancer between 1989 and 1996. S-TPA concentrations were measured by radioimmunoassay before treatment, at the end of treatment, and during follow-up evaluation. The upper normal limit of the test was set at 80 UI/L. RESULTS: With a specificity of 100%, the diagnostic sensitivity was 46%. Pretherapeutic S-TPA levels were significantly correlated with tumor stage (T2 v T3 and T4; P = .02), with nodal stage (N0 v N1 and N2; P = .00001), and with metastatic stage (M0 v M1; P = 10[-6]), but not with histologic grading (grade 1 and 2 v 3). In the subset of patients with normal pretherapeutic S-TPA levels, 95% had no residual disease at the end of treatment, compared with 53% of patients with initial elevated S-TPA (P = 10[-8]). Among patients who achieved a complete response, 27% experienced a relapse, with an increase of S-TPA in 72% of cases. The mean follow-up time was 20 +/- 17 months. For patients with normal pretherapeutic S-TPA levels, 3-year overall survival and disease-free survival rates were 76% and 67% respectively. These were 46% (P = .001) and 25% (P = 10[-7]), respectively, for patients with high pretherapeutic S-TPA. Multivariate analysis showed that S-TPA was an independent prognostic factor for survival (P = .03). CONCLUSION: In invasive bladder cancer, S-TPA level is correlated with initial tumor stage. It is a valuable parameter for follow-up evaluation and appears to be a prognostic factor in multivariate analysis.

[Value of postoperative radiotherapy in malignant tumors of the upper urinary tract. Apropos of a series of 26 patients]. / Intérêt de la radiothérapie postopératoire dans les tumeurs malignes de la voie excrétrice supérieure. A propos d'une série de 26 patients.

To evaluate the role of adjuvant radiation therapy in invasive transitional cell carcinoma of the upper urinary tract, we retrospectively reviewed a series of 26 patients who underwent radical surgery plus post-operative prophylactic irradiation for such a tumor. Between 1980 and October 1993, 18 men and eight women (mean age: 65 +/- 9 years) were treated for an invasive transitional cell carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15 patients (58%). The tumor was pathological stage B in 11 patients (42%) and stage C in 15 patients (58%). Tumor grade was 2 in ten patients, 3 in 15 and unknown in one. Nine patients had node involvement. All patients underwent surgery followed by radiation therapy to a total dose of 45 Gy to the tumor bed (23 patients) and/or regional nodes (18 patients). After a mean follow-up of 45 months, 13 patients (50%) were alive and 11 were disease-free. Local tumor relapse, nodal recurrence, metastasis and second urothelial location were noted in one, four (15%), 14 (54%) and eight patients (30%) respectively. Overall 5-year survival and 5-year disease-free survival were 49% and 30% respectively. Overall 5-year survival rates were 60% for stage B and 19% for stage C disease (P = 0.07), 43% for node-negative versus 15% for node-positive cancer (P = 0.04) and 90% for grade 2 and 0% for grade 3 tumors (P < 0.01). In this study using a radio-surgical approach, local control of disease and survival were similar to those reported previously in surgical series. Prophylactic post-operative radiation therapy is not recommended.

Phase II study of the oral cyclophosphamide and oral etoposide combination in hormone-refractory prostate carcinoma patients.

BACKGROUND: Hormonotherapy temporarily controls symptoms in 80% of patients with metastatic prostate carcinoma. Once progression occurs, no consensus exists on further therapy. Oral etoposide (VP-16) has shown clinical efficacy in advanced small cell lung carcinoma, breast cancer, germ cell tumors, and lymphomas, A synergistic effect between etoposide and alkylating agents such as estramustine was recently reported. We began a prospective Phase II study of an oral combination of cyclophosphamide (CPM) and VP-16 in patients with hormone-refractory [correction of refactory] prostate carcinoma (HRPC). METHODS: Patients were orally treated with CPM (100 mg/day) and VP-16 (50 mg/day) for 14 days every 28 days. Therapy continued until there was evidence of disease progression. RESULTS: From November, 1992, to February, 1995, 20 patients with HRPC were entered into the study. Patients were eligible if they had an ECOG performance status (PS) of 0 to 2. All of the patients presented with bone metastasis, and 70% presented with bone pain. Seventy-five percent had failed at least two hormonal manipulations. The mean duration of treatment was 5 months (range 2-12). Performance status improved in 26% of the patients, and bone pain was relieved in 71%. An objective response was defined as a decrease of 50% or more in the prostate-specific antigen (PSA) level. One patient demonstrated a complete response, and six patients had partial responses assessed by PSA plasma levels (objective response rate: 35%). The mean duration of response was 8 +/- 6 months (range: 2-24). Median survival was 11 months. Toxicities were minimal. CONCLUSIONS: The combination of oral CPM and VP-16 may be an active and well tolerated regimen for patients with HRPC.

[Infiltrating cancer of the bladder. Is concomitant radiochemotherapy an alternative to cystectomy?]. / Cancer infiltrant de la vessie. La radio-chimiothérapie concomitante peut-elle être une alternative a la cystectomie?

Infiltrating bladder cancer is an extremely severe condition causing death within 5 years due to metastatic extension in one-half of the patients whatever the treatment. It is well known that radiotherapy is successful in treating some patients while partial exeresis (open surgery or laparoscopic surgery) is effective in others. Current chemotherapy protocols (usually well-tolerated) increase the efficacy of radiotherapy but it is surprising that over the last 10 years, total cystectomy has become the first line treatment proposed for patients with infiltrating bladder cancer. The operation is a major procedure leading to an important morbidity and mortality. Since 1988, we have decided not to rely on total cystectomy for such patients, but rather to use a treatment protocol associating endoscopic exercise of the tumour and radiochemotherapy. Our results allow confirmation that this protocol can provide curative treatment in certain cases without removing the entire bladder. We thus suggest that systematic amputation of the bladder for cancer is an obsolete procedure and raise the question as to the usefulness of total cystectomy in this disease?

Postoperative radiation therapy in 26 patients with invasive transitional cell carcinoma of the upper urinary tract: no impact on survival?

PURPOSE: To evaluate the role of adjuvant radiation therapy in invasive transitional cell carcinoma of the upper urinary tract, we retrospectively reviewed a series of 26 patients who underwent radical surgery plus postoperative prophylactic irradiation for such a tumor. MATERIALS AND METHODS: Between February 1980 and October 1993, 18 men and 8 women (mean age 65 +/- 9 years, standard deviation) were treated for an invasive transitional cell carcinoma of the upper urinary tract. Tumor location was the renal pelvis in 15 patients (58%). The tumor was pathological stage B in 11 patients (42%) and stage C in 15 (58%). Tumor grade was 2 in 10 patients, 3 in 15 and unknown in 1. One patient had epidermoid metaplasia of urothelial cancer and 9 had node involvement. All patients underwent surgery followed by radiation therapy to a total dose of 45 Gy. to the tumor bed (23) and/or regional nodes (18). RESULTS: After a mean followup of 45 months 13 patients (50%) were alive and 11 were disease-free at analysis. Local tumor relapse, nodal recurrence and metastasis were noted in 1, 4 (15%) and 14 (54%) patients, respectively. All patients with nodal recurrence had metastasis. A secondary location was noted frequently (6 bladder, 1 contralateral renal pelvis and 1 urethral tumors). Overall 5-year survival rate and 5-year survival rate with no evidence of disease were 49% and 30%, respectively. Overall 5-year survival rates were 60% for stage B and 19% for stage C disease (p = 0.07), 49% for node-negative versus 15% for node-positive cancer (p = 0.04), and 90% for grade 2 and 0% for grade 3 tumors (p < 0.01). CONCLUSIONS: In our trial using a radio-surgical approach, local control of disease and survival rates were similar to those reported previously in surgical series. Prophylactic postoperative radiation therapy is not recommended except in prospective randomized studies.

[Simultaneous radiochemotherapy in locally advanced cancers of the cervix: a preliminary study]. / Radio-chimiothérapie concomitante dans les cancers du col utérin localement avancés: étude préliminaire.

We have designed a combined treatment strategy of bifractionated split course radiotherapy (RT) and concomitant chemotherapy (CT) to try to improve the results of RT in inoperable cervical carcinoma. After evaluation, patients were submitted to further radical surgery or additional RT-CT depending on the treatment results. Between January 1988 and January 1992, 25 patients with non metastatic inoperable disease entered in the protocol. The stage of the disease was: T3N0 4 patients, T3 with hydronephrosis seven patients, T3N1 12 patients, and T4N0 two patients. Nineteen patients received two courses of CT with fluorouracil (F), cisplatin (P) with or without etoposide. Pelvic RT was given twice daily (two fractions of 3 Gy) on days 1, 3, 15 and 17. A combination of F 400 mg/m2/d and P 15 mg/m2/d in continuous infusion with oral etoposide (100 mg/d) and hydroxyurea (500 mg/d) in 11 patients was delivered concomitantly on days 1-3 and 14-17. A clinical and radiological evaluation was performed four weeks later. Patients with objective response underwent radical hysterectomy (group A) and those with incomplete response received additional RT-CT protocol (group B). All patients had endocavitary brachytherapy at the end of treatment. After two cycles of CT there were four PR in 19 patients and 5 failures. After RT-CT there were 12 CR (48%) and eight PR. There was a relationship between disease status after RT-CT and response to initial CT in those 19 patients who received the neoadjuvant CT. Fifteen patients were in group A, six of whom had no histologically active disease in the post-operative sample. However all 15 patients were rendered free of disease. Ten patients were in group B, five of whom attained the clinical CR status. In total, 20 of 25 patients (80%) were in CR at the end of treatment. Six patients experienced pelvic recurrence and two patients distant metastases. Four of the five patients with incomplete response had evolutive disease. The overall survival is 60% and 36% at 1 and 2 years respectively after a median follow-up of 22 months (14-48 m). The protocol was tolerable. These results compare favorably with those of conventional RT and warrant further evaluation.