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Biomedical subjects

M Alfonsi

Publications and source records attributed to M Alfonsi.

13 recordsLinked to original sources

[Prostate cancer: has local radiation treatment had an impact on survival?].

Local control is an important goal in the treatment of prostate cancer. Firstly, it avoids the morbidity due to locoregional evolution (urethral obstruction, vascular compression, rectal or vesical involvement). Moreover, local control of the disease may decrease the mortality due to metastases disseminated from local relapse. Local control evaluation remains difficult: neither rectal examination nor imaging or prostate biopsies have an absolute value in diagnostic of local relapse. PSA increase does not permit to differentiate local from distant relapses. Recent developments in radiotherapy techniques allow dose escalation without major toxicity. Retrospective studies and one randomized study have shown that an increase from 70 to 80 Gy or more, improve biological relapse-free survival. In one randomized study comparing 70 to 78 Gy, the biochemical disease-free survival was improved from 69 to 79% at five years. Such an improvement can only be explained by an improvement of local control. The benefit in term of overall survival is not yet demonstrated and needs a longer follow-up and other studies. Another approach to improve local control is the association of a local radiotherapy with hormonal adjuvant therapy. Four randomized studies have been published for locally advanced prostate cancer. These studies have all demonstrated an improvement of local control, and a decrease of metastatic risk. The benefit in term of overall survival, observed in one of this trial, may be explained by the improvement of either local or distant control or both. Such therapeutic progress, associated with the development of prostate cancer screening should lead to a decrease of prostate cancer mortality for the next ten years.

Adenocarcinoma↗

[Are there physical, technical and morphological limits to conformational radiotherapy?].

Conformal radiotherapy results from several technical and data processing advances. The treatment planning and the daily treatments have benefited from a significant improvement of the quality control. However, all the steps of the process contain various limitations of varying effects. It appear important to identify, describe and exploit those limits to better drive the procedures and optimise the quality. Identifying the limits of the conformal radiotherapy should be an important help to implement intensity modulation radiotherapy.

Anthropometry↗

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.

Administration, Oral↗

[Stage III and IV cancers of the oropharynx: results of a randomized study of Gortec comparing radiotherapy alone with concomitant chemotherapy].

The aim of the study was to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV oropharynx carcinoma. A total of 226 patients have been entered in a phase III multicentric randomized trial comparing radiotherapy alone (arm A) to radiotherapy with concomitant chemotherapy (arm B). Radiotherapy was identical in the two arms, delivering, with conventional fractionation, 70 Gy in 35 fractions. In arm B patients received simultaneously 3 cycles of a four-day regimen containing carboplatin (70 mg/m2/d) and 5 fluorouracil (600 mg/m2/d) continuous infusion. The two arms were equally balanced regarding to age, gender, stage, performance status, histology, and primary tumor site. Radiotherapy compliance was similar in the two arms regarding to total dose, treatment duration and treatment interruption. Grade 3 and 4 mucositis rate was significantly higher in arm B (67% versus 36%). Skin toxicity was not different. Haematologic toxicity was higher in arm B on neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were respectively 51% versus 31% and 42% versus 20% for patients treated with combined modality versus radiation alone (p = 0.022 and 0.043). Local and regional control rate has been improved in arm B (66% versus 42%). The statistically significant improvement in overall survival obtained support the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx.

Combined Modality Therapy↗

Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma.

BACKGROUND: We designed a randomized clinical trial to test whether the addition of three cycles of chemotherapy during standard radiation therapy would improve disease-free survival in patients with stages III and IV (i.e., advanced oropharynx carcinoma). METHODS: A total of 226 patients have been entered in a phase III multicenter, randomized trial comparing radiotherapy alone (arm A) with radiotherapy with concomitant chemotherapy (arm B). Radiotherapy was identical in the two arms, delivering, with conventional fractionation, 70 Gy in 35 fractions. In arm B, patients received during the period of radiotherapy three cycles of a 4-day regimen containing carboplatin (70 mg/m(2) per day) and 5-fluorouracil (600 mg/m(2) per day) by continuous infusion. The two arms were equally balanced with regard to age, sex, stage, performance status, histology, and primary tumor site. RESULTS: Radiotherapy compliance was similar in the two arms with respect to total dose, treatment duration, and treatment interruption. The rate of grades 3 and 4 mucositis was statistically significantly higher in arm B (71%; 95% confidence interval [CI] = 54%-85%) than in arm A (39%; 95% CI = 29%-56%). Skin toxicity was not different between the two arms. Hematologic toxicity was higher in arm B as measured by neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were, respectively, 51% (95% CI = 39%-68%) versus 31% (95% CI = 18%-49%) and 42% (95% CI = 30%-57%) versus 20% (95% CI = 10%-33%) for patients treated with combined modality versus radiation therapy alone (P =.02 and.04, respectively). The locoregional control rate was improved in arm B (66%; 95% CI = 51%-78%) versus arm A (42%; 95% CI = 31%-56%). CONCLUSION: The statistically significant improvement in overall survival that was obtained supports the use of concomitant chemotherapy as an adjunct to radiotherapy in the management of carcinoma of the oropharynx.

Adult↗

[Results of long-term treatment of inoperable cancer of the bladder with cisplatin and concurrent irradiation: prognostic factors of local control and survival].

PURPOSE: Therapeutic strategies for muscle invasive bladder cancer are currently evolving. A recent European randomized study has shown that neoadjuvant chemotherapy does not improve the chance of cure or and radiotherapy would provide better results but there is a need to identify by prognostic factors patients who may benefit from such a conservative strategy. MATERIAL AND METHODS: One hundred and nine patients with localized muscle-invasive bladder cancer, who were not candidates for radical cystectomy, were treated with concomitant cisplatin and radiation therapy. Their mean age was 71. Thirty-six percent of the patients had T3B-4 tumors, and 37% had benefited from prior macroscopically complete transurethral resection (TUR). Pelvic irradiation consisted of 40 to 45 Gy and was followed by a boost to the bladder to a total dose of 55 to 60 Gy. Continuous infusion cisplatin (20 to 25 mg/m2/d for 5 days) was delivered during the second and fifth weeks of radiation therapy. RESULTS: Median follow-up was 73 months. The projected 5-year locoregional control rate was 43% for the 109 patients and 55% for the 86 patients with complete response. The projected overall 5-year survival rate was 36% for all patients and 44% for complete responders. Univariate analysis of prognostic factors was carried out for local control, and survival. The local control was statistically better in patients with good performance status, T2-3A, complete initial TUR, and in patients without hydronephrosis. In terms of overall survival, four factors were significant: the performance status, T-stage, absence of hydronephrosis, and complete response. By multivariate analysis, performance status, hydronephrosis and T-stage were significant factors for local control, while T-stage and complete response were the strongest determinants for survival. CONCLUSION: Concurrent cisplatin and radiation therapy is a potentially locally curative treatment for 43% of patients with muscle-invasive bladder cancer not candidates for radical surgery. Clinical T-stage and hydronephrosis have a significant and independent prognostic value on local control but appears not discriminant enough to select patients for conservative treatment.

Adult↗

[Current role of chemotherapy in the treatment of invasive cancers of the bladder].

Treatment of bladder carcinoma with cystectomy and or radiotherapy provide 5-year survival rates of 28-50%. Phase II chemotherapy trials have proven its efficacy with a partial and complete response rate of 20% and 10% respectively for drugs such as cisplatin or methotrexate. Recent phase III studies have demonstrated the superiority of associations such as CMV, CISCA or M-VAC with complete response rates of 28-39%. Neoadjuvant chemotherapy may increase local control and offer the possibility of conservative treatment after complete tumor regression (one third of cases). The positive effect of neoadjuvant chemotherapy on survival has not yet been demonstrated and randomized trials are now in progress. The concomitant association of cisplatin or fluorouracil with radiation therapy provides high complete response rates (65-88%) in all published studies. A longer follow-up period is necessary to confirm these results in terms of local control gain and survival benefit, but this strategy seems to constitute a major advancement for patients unable to undergo radical cystectomy. Further studies are needed before extending this conservative approach to less advanced invasive bladder carcinoma. Adjuvant chemotherapy may decrease metastasis rate, but survival benefit has not yet been definitively established by randomized studies.

Antineoplastic Combined Chemotherapy Protocols↗

High-dose methotrexate: a clinical and pharmacokinetic evaluation. Treatment of advanced squamous cell carcinoma of the head and neck using a prospective mathematical model and pharmacokinetic surveillance.

Some of 66 patients with head and neck tumors were treated with high-dose methotrexate monochemotherapy. The use of a prospective mathematical model with pharmacokinetic surveillance proved to be reliable, practical, and useful. By this means chemotherapy could be individualized, with a resultant marked reduction in the frequency and severity of toxicity. The onset of clinical toxic manifestations was significantly correlated with a poor therapeutic response and poor prognosis. The patients were classified in to three groups according to poor, intermediate, and good pharmacokinetic parameters calculated after an intravenous identification dose of methotrexate. These group allocations had a very high prognostic value with regard to toxicity, and especially to the quality of therapeutic response to high-dose methotrexate. They are suggested as useful guidelines in the prescription of high-dose methotrexate chemotherapy.

Adult↗

[Conservative treatment of anal canal carcinoma with external radiotherapy and interstitial brachytherapy, with or without chemotherapy: long-term results].

PURPOSE: A retrospective analysis of conservative treatment of anal canal cancers with external radiation therapy and interstitial brachytherapy with or without chemotherapy. PATIENTS AND METHODS: From 1986 to 1996, 69 patients were treated with external radiotherapy (40 Gy/20 fractions) and interstitial brachytherapy (20 Gy) after a mean interval of six weeks for a localized epidermoid carcinoma of the anal canal. Patients who did not complete the whole therapeutic sequence were not included. Forty-five patients received additional 5-fluorouracil- and/or mitomycin C-based chemotherapy regimen. RESULTS: Acute toxicity was acceptable. Complete response rate was 81%. Actuarial local control rate was at two and five years, 65% and 59% respectively (median follow-up: eight years). At two, five and ten years, actuarial colostomy rate was 26%, 33% and 33% respectively, and colostomy-free survival rates 61%, 47% and 37%. Overall survival at two, five and ten years was 81%, 65% and 53% respectively. Distant metastases occurred in 11 patients (16%). Prognostic factors for overall survival were performance status (PS) (79% survival at five years for patients with PS 0 versus 50% for patients with PS 1-3, P = 0.04) and tumor stage (80% at five years for T1-T2 versus 53% for T3-T4, P = 0.03). Overall treatment time less than 12 weeks and time interval between external radiotherapy and brachytherapy inferior than six weeks were associated with a better local control (P = 0.05). In multivariate analysis, these prognostic factors were not significant. CONCLUSION: These results confirm the efficacy of external radiotherapy and brachytherapy in the treatment of small anal canal cancers, and point out the need for improving treatment outcome of larger tumors.

Adult↗

[Conservative treatment of bladder cancers with radiotherapy and concurrent chemotherapy: results and perspectives].

Therapeutic strategies for muscle invasive bladder cancer are currently evolving. Transurethral surgery followed by concurrent chemotherapy and radiotherapy is the best treatment for patients not suitable for radical cystectomy. This conservative approach may be proposed for operable patients with similar survival than after cystectomy. Intermediate evaluation of response is necessary, as response is the more discriminant prognostic factor for local control. Non responders would be assigned for immediate cystectomy. Morbidity and results of salvage cystectomy are poorly evaluated and probably depending from time from initial treatment and dose of radiation.

Antineoplastic Combined Chemotherapy Protocols↗