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1.
Ann Oncol ; 21(4): 808-814, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19825885

ABSTRACT

BACKGROUND: The aim was to identify predictors of outcome in patients with localized prostate cancer treated with external beam radiotherapy (EBRT), with or without androgen deprivation therapy (ADT). MATERIALS AND METHODS: A total of 448 patients with prostate cancer received EBRT alone (n = 361, group 1) or ADT followed by EBRT (n = 87, group 2). In group 2, ADT was initiated 3 months before EBRT. After baseline prostate-specific antigen (PSA) determination (PSA(preRT)), PSA was assessed during the 6th week of the EBRT course (PSA(6wRT)) in group 1. In group 2, PSA was measured again 3 months after the start of ADT, before EBRT (PSA(ADT-preRT)). RESULTS: In group 1, median PSA(6wRT)/PSA(preRT) was 0.72 and median prostate-specific antigen velocity (PSAV) was -1.5 ng/ml/month. In the multivariate analysis, prognostic groups and PSA(6wRT)/PSA(preRT) (or PSAV) independently predicted biochemical failure (BF), clinical failure (CF), and prostate cancer-specific survival. In group 2, the median PSA(ADT-preRT) was 1.3 ng/ml. In the high-risk group, an undetectable PSA(ADT-preRT) (< or =0.2 ng/ml) predicted BF (P < 0.01) and CF (P = 0.007). CONCLUSION: A PSA decline 6 weeks after the start of EBRT when used as monotherapy and 3 months after the start of ADT in patients treated with combined ADT and EBRT is predictive of progression and specific survival.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Androgen Antagonists/therapeutic use , Prostate-Specific Antigen/blood , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/radiotherapy , Adenocarcinoma/blood , Adenocarcinoma/diagnosis , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/therapeutic use , Brachytherapy , Combined Modality Therapy , Down-Regulation , Early Diagnosis , Humans , Male , Middle Aged , Prognosis , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/diagnosis , Retrospective Studies , Survival Analysis , Time Factors , Treatment Failure
2.
Ann Oncol ; 17(6): 990-4, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16600984

ABSTRACT

BACKGROUND: The aim of the study was to evaluate the activity and the safety of the gemcitabine-oxaliplatin (GEMOX) combination as first-line treatment in advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract. MATERIALS AND METHODS: Patients with metastatic or unresectable TCC, PS < or =2, creatinine < or =1.5 upper limit of normal range (UNL) and measurable disease according to RECIST criteria were treated with a combination of gemcitabine (1500 mg/m(2)) followed by oxaliplatin (85 mg/m(2)) on day 1 and 15 of a 28-day cycle. RESULTS: A total of 123 cycles were administered to 30 patients (median 4, range 1-8). Three complete responses (CR) and 11 partial responses (PR) were observed. Overall response rate (ORR) was 47% (95% CI 28% to 66%). Median overall survival (OS) was 15 months (95% CI 8-31). Grade 3 and 4 neutropenia were reported in three and one patient, respectively; grade 3 anaemia in three patients; grade 3 and 4 thrombocytopenia in two and one patient, respectively; grade 1, 2 and 3 peripheral neuropathy in 14, 11 and two patients, respectively; grade 2 and 3 fatigue in 13 and seven patients respectively. CONCLUSIONS: The GEMOX combination is active in advanced/metastatic TCC with minimal toxicity and needs to be evaluated in a selected population of unfit patients and compared with other non-cisplatin-containing regimens.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Urologic Neoplasms/drug therapy , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/toxicity , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/physiopathology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Double-Blind Method , Drug Administration Schedule , Humans , Infusions, Intravenous , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Pain/prevention & control , Pain Measurement , Placebos , Treatment Outcome , Urologic Neoplasms/pathology , Urologic Neoplasms/physiopathology , Gemcitabine
3.
Bull Cancer ; 91(11): 871-3, 2004 Nov.
Article in French | MEDLINE | ID: mdl-15582891

ABSTRACT

Unresectable forms of HNSCC relapses occurring in a previously irradiated area are relatively common and may be difficult to manage from a therapeutic point of view. Full dose re-irradiation with concomitant chemotherapy constitutes an alternative to palliative chemotherapy. Indeed, the feasibility of this approach has been shown, and may be associated with a curative potential in a relatively low proportion of these relapses.


Subject(s)
Laryngeal Neoplasms/radiotherapy , Mouth Neoplasms/radiotherapy , Neoplasm Recurrence, Local/radiotherapy , Pharyngeal Neoplasms/radiotherapy , Clinical Trials, Phase II as Topic , Feasibility Studies , Humans , Hypopharyngeal Neoplasms/radiotherapy , Hypopharyngeal Neoplasms/surgery , Laryngeal Neoplasms/surgery , Mouth Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Oropharyngeal Neoplasms/radiotherapy , Oropharyngeal Neoplasms/surgery , Pharyngeal Neoplasms/surgery , Salvage Therapy
4.
Br J Cancer ; 90(1): 55-9, 2004 Jan 12.
Article in English | MEDLINE | ID: mdl-14710206

ABSTRACT

The aim of this study was to describe the incidence, clinical and histological characteristics, treatment and long-term follow-up of bilateral germ-cell tumours (BGCT) of the testis in order to determine in what respects they differ significantly from unilateral germ-cell tumours. In all, 31 patients with BGCT had metachronous tumours and 14 had synchronous tumours. Among the metachronous tumours, 61% occurred more than 5 years after the first tumour. The overall incidence of BGCT in patients with testicular germ-cell tumours (TGCT) was 1.9%. The incidence was 3.2% in patients presenting with a seminoma and 1.4 % in patients presenting with a nonseminomatous germ-cell tumour (NSGCT). Patients under 30 years of age at the time of the initial diagnosis had a higher incidence of bilateral tumours compared with older men. The outcome of BGCT was excellent. A high association was found between BGCT, sterility and suspected genetic risk factors for TGCT. These results argue against a systematic contralateral biopsy at diagnosis of first TGCT in all patients, but emphasise the importance of patient education and of the need to better identify patients at risk for a second TGCT. Therapeutic indications for synchronous BGCT, including conservative treatment, need to be better defined.


Subject(s)
Genetic Predisposition to Disease , Neoplasms, Multiple Primary/pathology , Neoplasms, Second Primary/pathology , Seminoma/pathology , Testicular Neoplasms/pathology , Adolescent , Adult , Humans , Incidence , Italy , Male , Middle Aged , Neoplasms, Multiple Primary/epidemiology , Neoplasms, Multiple Primary/genetics , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/genetics , Patient Education as Topic , Retrospective Studies , Risk Factors , Seminoma/epidemiology , Seminoma/genetics , Testicular Neoplasms/epidemiology , Testicular Neoplasms/genetics , Time Factors
5.
Cancer Radiother ; 8 Suppl 1: S24-8, 2004 Nov.
Article in French | MEDLINE | ID: mdl-15679243

ABSTRACT

The question of larynx preservation is central in the management of patients with a carcinoma of the larynx or hypopharynx, especially to preserve the main functions of the larynx. In early stages (T1-earlyT2) Larynx preservation can generally be obtained with partial surgery or radiotherapy. Some other approaches such as exclusive chemotherapy require further investigations. In locally advanced and infiltrating larynx/hypopharynx carcinomas, (advancedT2-T3), several ways have been used to preserve the larynx including exclusive radiotherapy which can be improved by modified fractionation and acceleration. The efficacy of radiotherapy can be also markedly increased by adding concomitant cisplatin based chemotherapy, as reported recently in a large randomized trial. An alternative approach consisted in using induction chemotherapy (cisplatin-5FU) and followed by a local treatment adapted to the response to chemotherapy. The combined analysis of 3 such randomized trials (GETTEC, Veteran et EORTC) showed that this approach has to be used with caution, and could be safer in good responders to induction chemotherapy. Finally, larynx preservation is generally not proposed in patients with deeply infiltrating tumors and or tumor invading the cartilage or soft tissue in the neck (T4).


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Hypopharyngeal Neoplasms/drug therapy , Hypopharyngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/drug therapy , Laryngeal Neoplasms/radiotherapy , Larynx , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Combined Modality Therapy , Dose Fractionation, Radiation , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Follow-Up Studies , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/surgery , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/surgery , Laryngectomy , Meta-Analysis as Topic , Pilot Projects , Radiotherapy Dosage , Randomized Controlled Trials as Topic , Survival Analysis , Time Factors
6.
Cancer Radiother ; 6(5): 310-9, 2002 Sep.
Article in French | MEDLINE | ID: mdl-12412370

ABSTRACT

The influence of thermoplastic masks used in clinical routine for patient immobilization in head and neck radiotherapy treatment on the absorbed skin dose has been investigated at Gustave-Roussy Institute. The measurements were performed in 60Co gamma-rays, 4 and 6MV X-rays and in 8 and 10MeV electron beams. Initially, the measurements were performed with thermoluminescent dosimeters (LiF) and a NACP chamber on a polystyrene phantom in order to study the influence of physical parameters (distance, field size, energy...) on first millimeters depth variation dose. The study was completed with in vivo measurements on 14 patients using various dosimeters (thermoluminescent detectors, diodes) in order to assess the increase of dose on first millimeters depth and to verify the delivered dose during treatment sessions (quality control). In treatment conditions, masks lead to an important increase of dose on the first millimeter in 60Co gamma-rays beams (dose value normalized to maximum of dose increase from 57.1% to 77.7% for 0.5 mm-water depth and from 78.5% to 88% for 1 mm-water depth); its contribution is less important in 4 and 6 MV X-rays beams (dose value normalized to maximum of dose increase from 49.5% to 63.2% for 0.5 mm-water depth and from 59% to 70.1% for 1 mm-water depth). Concerning 8 and 10 MeV electron beams, the normalized dose value increase respectively from 78.4% to 81.7% and from 82.2% to 86.1% for 0.5 mm-water depth. In vivo dosimetry enabled the quality control of delivered dose during treatment. Measured dose is in agreement within +/- 5% with the prescribed dose for 92.3% of cases. In routine, in vivo dosimetry allowed to quantify the increase of skin dose induced by thermoplastic masks for various energies of photon and electron beams as well as quality control.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Masks , Skin/radiation effects , Humans , Radiotherapy/adverse effects , Radiotherapy Dosage , Skin Absorption
8.
Ann Oncol ; 13(3): 475-9, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11996481

ABSTRACT

We report the case of a 37-year-old man in whom penile cancer was discovered while he was treated for AIDS 4 years after a human papillomavirus (HSV) infection. Despite initially localised disease with T1 N0 staging, he died of metastasis within 3 years. A brief review of the literature regarding HPV-related cancer in HIV-infected patients is presented and therapeutic options are discussed.


Subject(s)
Acquired Immunodeficiency Syndrome/pathology , Carcinoma, Squamous Cell/pathology , Papillomavirus Infections/pathology , Penile Neoplasms/pathology , Acquired Immunodeficiency Syndrome/therapy , Acquired Immunodeficiency Syndrome/virology , Adult , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/virology , Fatal Outcome , Humans , Male , Papillomaviridae/physiology , Papillomavirus Infections/therapy , Papillomavirus Infections/virology , Penile Neoplasms/therapy , Penile Neoplasms/virology
9.
Ann Otolaryngol Chir Cervicofac ; 119(1): 12-20, 2002 Feb.
Article in French | MEDLINE | ID: mdl-11965102

ABSTRACT

This is a retrospective study of laryngeal preservation in endolaryngeal cancer with induction chemotherapy and radiotherapy for good responders. Between 1985 and 1995, 104 patients were treated in Institut Gustave Roussy (87 patients) and in Limoges (17 patients). The overall survival for the whole population was 76% and 69% at 3 and 5 years respectively, with a 36% rate of laryngeal preservation. In this retrospective series of patients, the single prognostic factor affecting survival was arytenoid mobility before treatment (66% and 55% at 3 years vs 85% and 82% at 5 years; p<0.004). Loco-regional failures were higher (33% vs 15%, p<0.03), and laryngeal preservation was lower (18% vs 51%) among patients with a fixed arytenoid (49 pts), compared with patients with a non fixed arytenoid (55 pts) ). The percentages of patients with a fixed arytenoid could explain the conflicting results of the two randomized studies of laryngeal preservation in laryngeal cancer.


Subject(s)
Laryngeal Neoplasms/drug therapy , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/therapeutic use , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Arytenoid Cartilage , Bleomycin/administration & dosage , Bleomycin/therapeutic use , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Combined Modality Therapy , Data Interpretation, Statistical , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Humans , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/surgery , Laryngectomy , Leucovorin/administration & dosage , Leucovorin/therapeutic use , Lymphatic Metastasis , Neoplasm Metastasis , Prognosis , Radiotherapy Dosage , Retrospective Studies , Survival Analysis , Time Factors
10.
Cancer Radiother ; 5(3): 273-8, 2001 Jun.
Article in French | MEDLINE | ID: mdl-11446081

ABSTRACT

The paper deals with the recent improvements introduced in the most usual method applied in the Institut Gustave Roussy radiotherapy department for obtaining the anatomical data of patients treated for head and neck tumors. For each of these patients, five to seven transverses slices and a lateral radiographic film are taken from a Mecaserto simulator-CT. The anatomical representation of the patient sagittal plane is carried out from the digitalisation of the radiographic film on a Vidar Vxr-12 Plus film scanner and integrated into the Dosigray dose calculation programme in order to be used as a support for the laying out of the dose distribution in reference to the treatment. The sagittal anatomical representation obtained from the radiographic film digitalisation is compared with the one resulting from the interpolation between a limited number of irregularly-spaced transverse slices taken on the simulator-CT. The method using the simulator-scanner transverse slices and the radiographic film digitalisation represents an interesting alternative for obtaining an anatomy simulation representative of the patient in hospitals where a scanner is not available full-time for the needs of the radiotherapy process.


Subject(s)
Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Tomography, X-Ray Computed , Cancer Care Facilities , France , Humans
11.
Cancer ; 91(11): 2071-6, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11391587

ABSTRACT

BACKGROUND: The purpose of this study was to analyze the tolerance and efficacy of full dose reirradiation combined with chemotherapy in patients with head and neck carcinoma (HNC) with a high risk of recurrence after salvage surgery. METHODS: Between 1991 and 1996, 25 patients having a recurrence or a second primary tumor in a previously irradiated area (> 45 grays [Gy]) were entered in this prospective study. All of them received salvage surgery and had a positive surgical margin and/or lymph node involvement with capsular rupture (N+R+). Adjuvant radiochemotherapy was given, delivering 60 Gy per 30 fractions with concomitant hydroxyurea and 5-fluorouracil. The median total cumulative dose of the 2 irradiations was 118 Gy. The median follow-up after the second irradiation was 66 months. RESULTS: During the reirradiation course, Grade 3 and 4 mucositis were observed in 40% and 12%, respectively. Analysis of late effects (> 6 months after reirradiation) showed that 16% of the patients had osteoradionecrosis and 40% had Grade 2-3 cervical fibrosis (Radiation Therapy Oncology Group scoring system). The patterns of failure were as follows: local only (n = 9), lymph node only (n = 2), local and lymph node only (n = 1), and metastatic (n = 4). The 4-year survival rate after reirradiation was 43% (95% confidence interval, 25-62). CONCLUSIONS: Full dose reirradiation combined with chemotherapy after salvage surgery in high risk patients with HNC was feasible with an "acceptable" toxicity and led to a relatively good 5-year survival rate. These results prompted the authors to initiate a multicentric randomized trial that is ongoing (GETTEC-GORTEC 99-01) to evaluate the benefit of adjuvant radiochemotherapy in these types of patients.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adenocarcinoma/surgery , Adult , Aged , Carcinoma, Squamous Cell/surgery , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Head and Neck Neoplasms/surgery , Humans , Hydroxyurea/administration & dosage , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Radiotherapy/adverse effects , Risk Factors , Salvage Therapy , Survival Analysis
12.
Urol Oncol ; 6(2): 49-52, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11166620

ABSTRACT

We report five distinct cases of apparently metachronous extragonadal and gonadal germ cell tumors (GCT) occurring in the same patient. Two patients had metachronous GCT of the central nervous system and the testis. One of these patients had been successfully treated for a germinoma of the pineal gland and developed a nonseminomatous GCT of the testis 10 years later. The second patient had a primary seminoma of the testis treated by orchiectomy followed by radiotherapy and developed a germinoma of the sphenoidal sinus 17 months later. Three other patients had an apparently metachronous retroperitoneal and testicular GCT with 22, 44, and 66 months elapsing, respectively, between the first and second neoplasms. These cases suggest that the remaining testis is not only at risk for a second primary GCT, but that a second GCT may emerge at an extragonadal site. A genetic predisposition may account for some of these cases and the occurrence of bilateral testicular GCT. In none of these cases, however, could we ascertain whether testicular GCT was truly a second primary or a relapse of a "primary" retroperitoneal GCT in our cases.

13.
Crit Rev Oncol Hematol ; 34(3): 195-203, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10838265

ABSTRACT

Elderly patients represent the most rapidly growing subgroup of the patient population in France and in the majority of industrialized countries. The effect of age in terms of the prognosis and response to treatment remains unclear. The management strategy (curative versus palliative) for head and neck cancer in the elderly has given vent to divergent opinions and controversies in several respects (the type and quality of treatment, quality of life and economic consequences). This review only focuses on the radiotherapy schedule and head and neck cancers. We compare aged patients with head and neck cancer to younger patients in terms of clinical features, tumor biology, type of treatment, side effects and response. We conclude that if the patient is in a good general condition following a complete evaluation of the cancer, physicians should propose curative treatment with radiotherapy because retrospective trials demonstrate that response in older patients when treated aggressively is comparable to that of younger patients. However, specific trials concerning aged patients with head and neck cancer, quality of life and radiotherapy are warranted.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Age Factors , Aged , Female , Head and Neck Neoplasms/pathology , Humans , Male , Quality of Life , Radiotherapy/adverse effects , Radiotherapy/psychology , Risk Assessment
14.
J Clin Oncol ; 18(6): 1324-30, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10715304

ABSTRACT

PURPOSE: To review incidence and analyze profile of long-term complete responders among patients with undifferentiated carcinoma of nasopharyngeal type (UCNT) treated at a single institution. PATIENTS AND METHODS: We present a cohort of 20 long-term unmaintained complete responders to chemotherapy for metastatic UCNT treated at the Institut Gustave Roussy between April 1978 and November 1996. A patient was considered a long-term survivor if he or she was disease-free for more than 36 months without treatment after obtaining a complete response by chemotherapy. Patient characteristics were as follows: sex, 17 men and three women; median age, 28 years (range, 9 to 62 years); median World Health Organization performance status, 1; and initial tumor-node-metastasis stage (International Union Against Cancer-American Joint Committee on Cancer, 1987) of T3 to T4, 60%, and of N2b to N3, 75%. Epstein-Barr virus serology was characteristic in 19 patients. Of 16 pretreated patients, 11 were pretreated by radiotherapy alone and five by chemotherapy and radiotherapy. Thirteen patients had metastatic relapses of locally controlled UCNT. Tumor sites were bone in 15 patients, lung in four, and liver (biopsy-proven) in two. Chemotherapy included the following: cisplatin, bleomycin, and fluorouracil in five patients; bleomycin, epirubicin, and cisplatin in seven patients; fluorouracil, mitomycin, epirubicin, and cisplatin in four patients; and fluorouracil, bleomycin, epirubicin, and cisplatin in one patient. Three patients were treated with platinum-based regimens before 1985. Patients received a median of six cycles (range, three to 13). Thirteen patients with bone metastases received consolidating radiotherapy. RESULTS: As of June 1999, 14 of 20 patients were still alive with no evidence of disease after treatment (disease-free survival time, 82+ to 190+ months), three patients died of other causes while in complete response at 61, 109, and 208 months after treatment, and three patients died of disease at 42, 89, and 115 months after treatment. Long-term complete responses were obtained in both bone and visceral disease. CONCLUSION: Our data support a curative role for chemotherapy in metastatic UCNT and are a major incentive to continue research for better combinations to increase the percentage of patients with metastatic UCNT who attain complete responses and long-term survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Nasopharyngeal Neoplasms/drug therapy , Survivors , Adolescent , Adult , Carcinoma/radiotherapy , Carcinoma/secondary , Child , Disease-Free Survival , Female , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/radiotherapy
15.
Int J Radiat Oncol Biol Phys ; 46(5): 1105-8, 2000 Mar 15.
Article in English | MEDLINE | ID: mdl-10725619

ABSTRACT

PURPOSE: The aim of this study was to assess whether amifostine could minimize acute mucositis induced by a very accelerated irradiation regimen in patients with advanced head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: Between May 1996 and February 1998, 26 patients with an inoperable nonmetastatic Stage IV HNSCC were entered in this study. The treatment consisted of very accelerated radiotherapy given 64 Gy in 3.5 weeks. The patients were randomized to receive or not 150 mg/m(2), amifostine (Ethyol, U.S. Bioscience) 15-30 min prior to each radiation session. RESULTS: Of the 13 patients who received amifostine, definitive interruption of amifostine occurred in 5 cases (38%), due to tolerance problems (vomiting, liver enzyme elevation, generalized erythema). The distribution of Grade 4 mucositis (WHO) was 1 case versus 8 cases, with and without amifostine, respectively. The mean duration of "at least Grade 3" mucositis (WHO) was 25.1 days versus 49.2 days with and without amifostine (p = 0.03). In the amifostine group, 11/13 of the patients required a feeding tube (nasogastric tube or medical gastrostomy), because of acute mucositis, whereas in the control group a feeding tube was necessary in all cases. The mean duration of the use of this feeding tube was 1 month versus 2.5 months with and without amifostine respectively (p < 0.01). Local-regional control was not different between both arms with a median follow-up of 15 months. CONCLUSION: Despite the limited number of patients, this pilot randomized study suggests that amifostine was able to markedly reduce the severity and duration of mucositis induced by very accelerated radiotherapy. However, the tolerance of this twice daily amifostine schedule was relatively poor.


Subject(s)
Amifostine/therapeutic use , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/radiotherapy , Radiation-Protective Agents/therapeutic use , Stomatitis/prevention & control , Adult , Aged , Amifostine/adverse effects , Carcinoma, Squamous Cell/pathology , Drug Administration Schedule , Drug Eruptions/etiology , Feasibility Studies , Head and Neck Neoplasms/pathology , Humans , Middle Aged , Neoplasm Staging , Radiation Injuries/etiology , Radiation Injuries/prevention & control , Radiation-Protective Agents/adverse effects , Radiotherapy Dosage , Stomatitis/etiology
16.
Br J Cancer ; 83(12): 1594-8, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11189100

ABSTRACT

The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing neoadjuvant chemotherapy followed by loco-regional treatment to the same loco-regional treatment without chemotherapy. The loco-regional treatment consisted either of surgery plus plus radiotherapy or of radiotherapy alone. Three cycles of chemotherapy consisting of Cisplatin (100 mg/m2) on day 1 followed by a 24-hour i.v. infusion of fluorouracil (1000 mg/m2/day) for 5 days were delivered every 21 days. 2-3 weeks after the end of chemotherapy, local treatment was performed. The trial was conducted by the Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC). A total of 318 patients were enrolled in the study between 1986 and 1992. Overall survival was significantly better (P = 0.03) in the neoadjuvant chemotherapy group than in the control group, with a median survival of 5.1 years versus 3.3 years in the no chemotherapy group. The effect of neoadjuvant chemotherapy on event-free survival was smaller and of borderline significance (P = 0.11). Stratification of the results on the type of local treatment, surgery plus radiotherapy or radiotherapy alone, did not reveal any heterogeneity in the effect of chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Oropharyngeal Neoplasms/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Disease-Free Survival , Fatigue/chemically induced , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leukopenia/chemically induced , Male , Middle Aged , Nausea/chemically induced , Neoadjuvant Therapy , Oropharyngeal Neoplasms/radiotherapy , Oropharyngeal Neoplasms/surgery , Proportional Hazards Models , Thrombocytopenia/chemically induced , Treatment Outcome , Vomiting/chemically induced
17.
Cancer ; 86(7): 1101-8, 1999 Oct 01.
Article in English | MEDLINE | ID: mdl-10506692

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the toxicity and efficacy of the combination of 5-fluorouracil, bleomycin, epirubicin, and cisplatin (FBEC) in the treatment of patients with undifferentiated carcinoma of nasopharyngeal type (UCNT). The study included patients with metastatic or recurrent disease (Group A) and previously untreated patients with locally advanced nonmetastatic disease (T >/= 3 or any T, N >/= 2, M0, according to 1987 criteria of the International Union Against Cancer and the American Joint Committee on Cancer (Group B). METHODS: From January 1992 to November 1996, 49 patients with histologically proven UCNT were treated with intravenous (i.v.) 5-fluorouracil (700 mg/m(2)/day by continuous infusion for 4 days), epirubicin (70 mg/m(2) i.v. on Day 1), Bleomycin (10 mg i.v. bolus on Day 1 followed by 12 mg/m(2)/day by continuous infusion for 4 days), and cisplatin (100 mg/m(2) on Day 5); this regimen was repeated every 21 days. Six cycles were given to Group A (26 patients), with bleomycin omitted during the last 3 cycles. In Group B (23 patients), only 3 cycles were given, followed by conventional radiotherapy (70 gray for 7 weeks). RESULTS: Of the 26 patients entered in Group A, 23 were evaluable for response. Nine complete responses (CRs) and 9 partial responses (PRs) were assessed, for a 78% objective response rate (ORR) (95% CI: 56-92). Three patients are alive with no evidence of disease after 43, 61, and 73 months, respectively. These patients achieved a CR with chemotherapy followed by consolidating radiotherapy to their target lesions. In Group B, the ORR was 91.5%, with 5 CRs (22%) and 16 PRs (69.5%) assessed in the 23 patients. Three months after the end of radiotherapy, the ORR was 87% (20 patients). After a median follow-up of 51 months (range, 24-67 months), 15 patients (65%) are alive without evidence of disease. Forty percent of cycles (51% in Group A, 25% in Group B) resulted in Grade 4 neutropenia, with fever and/or sepsis in 9.5%. Mucositis was seen in 42% of pretreated patients. There were 3 treatment-related deaths (2 from complications of infection and 1 bleomycin fibrosis at a total dose of 160 mg/m(2)), all of them in Group A. CONCLUSIONS: The FBEC regimen has good activity, with durable responses in patients with locally advanced, metastatic, or recurrent UCNT. This regimen is safe for patients with locally advanced disease, but close follow-up and supportive measures are needed when it is used to treat those with metastatic or recurrent disease.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Nasopharyngeal Neoplasms/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Bleomycin/adverse effects , Carcinoma/mortality , Carcinoma/secondary , Cisplatin/administration & dosage , Cisplatin/adverse effects , Drug Administration Schedule , Epirubicin/administration & dosage , Epirubicin/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Follow-Up Studies , Humans , Infusions, Intravenous , Male , Middle Aged , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/secondary , Neoplasm Recurrence, Local , Radiotherapy/methods , Survival Rate , Treatment Outcome
18.
J Clin Oncol ; 16(11): 3556-62, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9817275

ABSTRACT

PURPOSE: To review our experience using full-dose external reirradiation given with a curative intent for patients with unresectable head and neck carcinoma (HNC). PATIENTS AND METHODS: Between January 1980 and December 1996, 169 patients who presented with unresectable nonmetastatic HNC in a previously irradiated area were included in this series. The median time between the first and the second irradiation was 33 months. Reirradiation protocols were as follows: radiotherapy alone (65 Gy over 6.5 weeks at 2 Gy/d), 27 patients; Vokes protocol, ie, five to six cycles of radiotherapy (median total dose, 60 Gy; 2 Gy/d) with simultaneous fluorouracil (5-FU) and hydroxyurea, 106 patients; and bifractionated radiotherapy (median total dose, 60 Gy; 2 x 1.5 Gy/d) with concomitant mitomycin, 5-FU, and cisplatin, 36 patients. The median cumulative dose of the two irradiations was 120 Gy. Eighty-five percent of the tumors were squamous cell carcinoma, 14% undifferentiated carcinoma of nasopharyngeal type, and 1% adenocarcinoma. Forty-four percent were local recurrences, 23% nodal recurrences, 14% both local and nodal, and 19% second primary tumors. RESULTS: Mucositis grade 3 (World Health Organization [WHO]) was found in 32% and grade 4 in 14% of cases. Four patients presented with neutropenia or thrombocytopenia (grade 3 or 4 WHO). Late toxicities (> 6 months) were as follows: cervical fibrosis (grade 2 to 3 Radiation Therapy Oncology Group [RTOG]), 41%; mucosal necrosis, 21%; osteoradionecrosis, 8%; and trismus, 30%. Five patients died of carotid hemorrhage, apparently in complete remission. Six months after the onset of reirradiation, 37% of patients were in complete response. Patterns of failure were local only (53%), nodal only (20%), metastatic only (7%), and multiple (20%). Median follow-up time was 70 months. Overall survival rate (Kaplan-Meier) was 21% (95% confidence interval [CI], 15% to 29%) at 2 years and 9% (95% CI, 5% to 16%) at 5 years. Median survival time was 10 months for the entire population. Thirteen patients, of whom 12 were treated with the Vokes protocol, were long-term disease-free survivors. In a multivariate analysis, the volume of the second irradiation was the only factor significantly associated with the risk of death: relative risk=1.8 (95% CI, 1.13 to 5.7) (P=.01). CONCLUSION: Full-dose reirradiation combined with chemotherapy was feasible in patients with inoperable HNC. The incidence and severity of late toxicity was markedly increased in comparison to that observed after the first irradiation. Median survival was better than that generally obtained using palliative chemotherapy alone. A small proportion of patients were long-term disease-free survivors.


Subject(s)
Carcinoma/radiotherapy , Head and Neck Neoplasms/radiotherapy , Adult , Age Factors , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Chemotherapy, Adjuvant , Dose Fractionation, Radiation , Female , Head and Neck Neoplasms/drug therapy , Humans , Male , Middle Aged , Mucous Membrane/radiation effects , Neoplasm Recurrence, Local/radiotherapy , Prognosis , Radiotherapy/adverse effects , Retreatment , Sex Factors , Stomatitis/etiology , Survival Analysis
19.
Eur J Cancer ; 34(6): 856-61, 1998 May.
Article in English | MEDLINE | ID: mdl-9797698

ABSTRACT

The study was performed to assess the effect of accelerated radiotherapy on oxygenation of primary tumours and metastatic nodes in patients with advanced head and neck tumours. In 14 patients with head and neck tumour, oxygen tension (pO2) was evaluated in normal tissues and tumours (primary tumour or metastatic neck node) before (0 Gy) and after 2 weeks (32 Gy) of accelerated radiotherapy (70 Gy in 3.5 weeks, with three daily fractions). Radiotherapy was combined with carbogen breathing in 5 patients. pO2 was measured using a polarographic technique. For pooled normal tissues, median pO2 was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values (< 2 mmHg) represented 20% of the recorded values before treatment and 10% after 2 weeks. The relative increase in tumour oxygenation was more pronounced for primary tumours (median pO2 12 mmHg before treatment versus 26 mmHg after 2 weeks, P < 0.05) than for metastatic nodes (respectively, 20 and 27 mmHg P = 0.1). For the 5 patients who breathed carbogen during accelerated radiotherapy, the median pO2 was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P = 0.05). Very low pO2 values, corresponding to tumour hypoxia, were found in the tumours (primary and metastatic neck nodes) prior to accelerated treatment. During the first 2 weeks of accelerated treatment, an increase in median pO2 was found in nine of the 14 tumours, together with a decrease in the frequency of very low values.


Subject(s)
Mouth Neoplasms/radiotherapy , Oropharyngeal Neoplasms/radiotherapy , Oxygen/metabolism , Aged , Carbon Dioxide/administration & dosage , Combined Modality Therapy , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Mouth Neoplasms/chemistry , Oropharyngeal Neoplasms/chemistry , Oxygen/administration & dosage , Partial Pressure
20.
Ann Otol Rhinol Laryngol ; 107(7): 581-7, 1998 Jul.
Article in English | MEDLINE | ID: mdl-9682853

ABSTRACT

The free jejunal autograft (FJA) has become a common procedure for pharyngeal reconstruction after circumferential pharyngolaryngectomy. In order to evaluate the postoperative outcome and the functional and carcinologic results, we retrospectively reviewed 83 cases of reconstruction with FJA. Fifty-one patients had received no prior radiotherapy, and 25 had received prior radiotherapy for their hypopharyngeal tumor or for another previous primary. Seven patients underwent a secondary reconstruction. In the postoperative course, there were 2 postoperative deaths, 4 graft failures (5%), and 11 salivary fistulas. The median time to removal of the nasogastric tube was 16 days, and to discharge, 23 days. Forty-eight patients received postoperative radiotherapy, with good tolerance. At 1 year postoperatively, 98% of the patients were able to eat a solid or soft diet. The postoperative radiotherapy did not impair the quality of the functional results in a long-term assessment. The vocal results were disappointing. The 3-year survival rate was 40%. The main carcinologic failures (45 patients) were locoregional recurrences (20 patients) and metastasis, which was the cause of death in 34% of the cases. It seems clear that FJA allows one-stage reconstruction and good swallowing rehabilitation, tolerates postoperative radiotherapy, and increases the quality of life in these patients with a poor prognosis.


Subject(s)
Jejunum/transplantation , Laryngectomy/methods , Larynx/surgery , Pharyngectomy/methods , Pharynx/surgery , Adolescent , Adult , Aged , Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Carcinoma/radiotherapy , Carcinoma/surgery , Cisplatin/therapeutic use , Combined Modality Therapy , Female , Fluorouracil/therapeutic use , Follow-Up Studies , Humans , Hypopharyngeal Neoplasms/drug therapy , Hypopharyngeal Neoplasms/radiotherapy , Hypopharyngeal Neoplasms/surgery , Male , Middle Aged , Retrospective Studies
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