[Survey by SFRO, SNRO and AFPPE about the evolution of the radiation therapist profession in France]. / Enquête SFRO­SNRO­AFPPE sur l'évolution du métier de manipulateur exerçant en radiothérapie en France.

PURPOSE: As part of the multidisciplinary team, radiation therapists are in charge of elements of treatment preparation and delivery of radiotherapy to cancer patients. Helping scientific and technological improvements, more and more patients with cancer were treated with radiotherapy including hypofractionnated radiotherapy, that explain the increase of demands on services. The professional impacted by this increase of demands are radiation oncologists and medical physicists. The opportunity to push forward the radiation therapist's competencies appears with the possibility to shift them some tasks. In this context, a first work was performed with objectives to have an overview of the tasks shifted to radiation therapists in France, the tasks that they could perform but also to evaluate some criteria of job satisfaction. MATERIAL AND METHODS: The committee of "new status and value of status" including six radiation oncologists (the French society of radiation oncology [SFRO] et national union of radiation oncologists [SNRO]) and six radiation therapists committee members of the French association of radiation therapists (AFPPE), built a questionnaire including three parts: demographic characteristics, tasks shifted and job satisfaction criteria. In total, the questionnaire included 19 questions and 24 items assessed with a four point-Likert scale (ranging from "completely disagree" to "completely agree"). This survey, formatting with google form, was tested by the committee members and the final version was sent to the SFRO, AFPPE and SNRO members, before being disseminated on the social networks. RESULTS: From November 18th 2022 to December 31st 2022, 492 responses were received (response rate=18.3%): 55 % of the respondents had at least 11 years of experience in radiotherapy. The respondents worked in different type of health facilities (36 % in specialized cancer centres, 19.5 % in private centers, 17.5% in university and general hospital, 10.2% in general hospital). More than » of the respondents had a teaching lecturer activity, 20% had a management team activity and a research activity for 18%. Less than 10% of the respondents had another degree than that of radiation therapist: university degree (n=27), degree in dosimetry (n=11) and master (n=3). More than 76% would like to be trained and to have access to the advanced practice, more than 50% would like expend competencies with a university degree, 30% with a master and 67% would like to participate in research. Forty-two percent of the respondents were involved in a task shifting (excluding decree relating to acts and activities carried out by radiation therapists) and among the radiation therapists non-involved, 63% would be interested in being. Regarding job satisfaction, 53% of the respondents were satisfied with their job and their salary and 68% believed that their job occupation is in line with their professional aspirations. More than 2/3 of the respondents described a significant workload and mental load, 53% thought to have time for their patient care and 70% felt some organisational difficulties. CONCLUSION: This survey shows: (i) A significant involvement of radiation therapists in the task shifting; (ii) A very strong demand for career development, in particular with existing degrees or to be created degree such as advanced practice; and (iii) The need to reinforce a job satisfaction for almost the half of the respondents, linked to a workload, a mental load and some organisational difficulties.

[Radiation therapists shortage in France: Organizational consequences and difficulties in deploying new missions and/or tasks delegation]. / Métier de manipulateur en radiothérapie en tension en France : conséquences organisationnelles et difficultés à déployer de nouvelles missions et/ou délégation de tâches.

PURPOSE: Radiation therapists shortage has been evaluated at national level in France, specifically in oncology radiotherapy, in terms of: (i) organizational adaptations, (ii) impact on patients care, and (iii) difficulties in deploying new missions and/or tasks delegation. MATERIALS AND METHODS: French professional organisations representing radiation therapists - SFRO, SNRO and AFPPE - sent their members a national survey (ten questions on 32 items). RESULTS: From 18 November 2022 to 31 December 2022, 55 responses were received (response rate: 31%) from radiotherapy managers or department heads; 51% had a structure comprising three to five treatment rooms (receiving 500 to 1000 patients per year [36%], or 1500 to 2000 patients per year [33%]). Activities performed were intensity-modulated radiotherapy (100%), stereotaxic radiotherapy (85%), brachytherapy (40%), adaptive radiotherapy (34%). These structures described consequences in closing machine time for 25% of them (reduction of the hourly volume greater than 10% in 57%) with the following consequences in the last 6 months: (i) an extension of the period of medical care (78%), a closing of one or more accelerators (50%) and the development of moderate hypofractionation scheme or extreme hypofractionation (50%). In current functioning, linear accelerators can deliver treatments with a team of two radiation therapists per room for a short day (43%) or two to four radiation therapists per room teams for a long day (40%). During the last 6 months, there has been a 10% increase in linear accelerators operating with a single team. (ii) regarding treatment planning: 16.4% reported a decrease in the opening amplitude (less than 20% in 44% of cases, from 20 to 50% in 33 % of cases). The initial scheduling of appointments for radiotherapy sessions was carried out by radiation therapists in 84% of the departments in current functioning (0.1 to 1 FTE dedicated to this activity in 62% of the departments). Over the last 6 months, there has been a clear reduction in the number of dedicated FTEs: [FTE=0.1 to 1]=-8%; [FTE=0]=+7%. (ii) Regarding tasks delegation (excluding the decree on acts and activities carried out by the radiation therapist): organ at risk delineation is partially performed by radiation therapist in 26% of the centres; caregiver support time in 78% (56% totally or 22% partially). This activity has been reduced by 42%. Seventy-five percent of departments want to develop new techniques, patient-centered approaches (44%), implement task delegation (organ at risk delineation: 58%; weekly consultations: 67%; positioning imaging validation: 71%), and 78% of departments are interested in developing advanced radiotherapy practice. However, the number of radiation therapists is considered insufficient in their implementation in 76% of cases (one to two FTE missing for 72% of structures). CONCLUSION: This survey shows a significant impact of radiation therapist shortage in radiotherapy oncology care (treatment delays, access to caregiver support time, workload on treatment teams), and represents a major obstacle to the development of radiotherapy structures.

Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

Assessment of tumor angiogenesis as a prognostic factor of survival in patients with oligodendroglioma.

According to World Health Organization (WHO) and Daumas-Duport grading systems, progression of oligodendrogliomas (ODGs) to a higher grade (WHO grade III, grade B) is associated with increased angiogenesis. Based on multivariate assessment of molecular, pathological, and radiological parameters, we further assessed the influence of tumor angiogenesis on tumor progression and patient survival. Patients with a diagnosis of ODG, consecutively treated in a single institution, were reviewed and reclassified according to WHO and Daumas-Duport grading systems. MRI scans were reviewed to assess contrast enhancement and necrosis. Tissue sections were used for pathology review and to evaluate immunostaining of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGF-R), Ki-67, and CD34. Multivariate analysis was performed to assess the impact of tumor angiogenesis-related pathological and radiological factors on patient survival. One hundred thirty-four patients with pure ODG were included in this study. Multivariate analysis identified four independent poor prognostic factors: necrosis, absence of seizure, increased vascularization, and age >55 years. A subgroup of patients with tumor necrosis, increased vascularization, and absence of seizures had a significantly worse outcome than predicted, with a median overall survival of 14.2 months. VEGF expression was significantly higher in this subgroup and correlated with disease progression regardless of histologic grade. Based on the presence of radiological or pathological necrosis, contrast enhancement or endothelial hyperplasia, and absence of seizures, a high risk group of ODG can be identified with significantly worse overall survival. Also, VEGF over-expression in ODG constitutes an early marker for predicting tumor progression.

[Indications and outlooks of radiohormonal therapy of high-risk prostate cancers]. / Indications et perspectives de l'hormonoradiothérapie des cancers de prostate à haut risque.

Prostate cancer is a sensitive adenocarcinoma, in more than 80% of cases, to chemical castration, due to its hormone dependence. Locally advanced and/or high-risk cancer is defined based on clinical stage, initial prostate specific antigen serum concentration value or high Gleason score. Hormone therapy associated with radiation therapy is the standard of management and improves local control, reduces the risk of distant metastasis and improves specific and overall survival. Duration of hormone therapy, dose level of radiation therapy alone or associated with brachytherapy are controversial data in the literature. The therapeutic choice, multidisciplinary, depends on the age and comorbidity of the patient, the prognostic criteria of the pathology and the urinary function of the patient. Current research focuses on optimizing local and distant control of these aggressive forms and incorporates neoadjuvant or adjuvant chemotherapy and also new hormone therapies.

Patterns of practice of androgen deprivation therapy combined to radiotherapy in favorable and unfavorable intermediate risk prostate cancer. Results of The PROACT Survey from the French GETUG Radiation Oncology group.

PURPOSE: The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. MATERIALS AND METHODS: A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. RESULTS: Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA>15 (77%) and/or Gleason 7 (4+3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. CONCLUSION: To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug.

[Ductal carcinoma in situ: role of the boost]. / Radiothérapie des carcinomes canalaires in situ: impact du complément d'irradiation du lit tumoral.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

Topotecan preceded by oxaliplatin using a 3 week schedule: a phase I study in advanced cancer patients.

Combinations of topoisomerase I (topo I) poisons and platinum derivatives have synergistic antitumoral effects. However, their clinical development is limited by supra-additive haematological toxicity. The aim of this study was to determine whether sustained doses of topotecan and oxaliplatin could be achieved using a synergistic sequence. 34 advanced cancer patients and 186 cycles were evaluable for toxicity over five dosing levels. Oxaliplatin at 85-110 mg/m(2) was given on day 1, followed by topotecan 0.5-1.25 mg/m(2)/day x 5 from day 1 to 5, every 3 weeks. Plasma pharmacokinetics (PK) of total and ultrafiltrable platinum, total and lactone forms of topotecan were determined in the first cycle. The dose-limiting toxicity (DT) was identified as grade 4 thrombocytopenia. The occurrence of grade 4 thrombocytopenia did not correlate with topotecan PK, but it did with the patient's characteristics. Severe thrombocytopenia was seen in 1/8 of patients without clinical or biological evidence of malnutrition, with a creatinine clearance higher than 1 ml/s, and no more than two previous chemotherapy regimens, while it was seen in 8/10 patients with one of these characteristics (P<0.004). In conclusion, the recommended doses of oxaliplatin 110 mg/m(2) and topotecan 1 mg/m(2)/day, every 3 weeks can be administered to patients with a favourable general status and pretreatment characteristics and a phase II study is worthwhile in ovarian cancer patients.

Differential absorption of vitamin D3 and 1,25-dihydroxyvitamin D3 by intestinal jejunal cells of the rat.

An intestinal perfusion technique is reported for the study of the differential absorption of vitamin D3 and its active metabolite, 1,25-dihydroxyvitamin D3, through intact jejunal segments of rats. Samples of introduced and collected perfusates, intestinal homogenates, and portal blood were assayed for [14C]vitamin D3 or [3H]1 alpha,25-dihydroxyvitamin D3 content at specified time intervals in control rats and in rats injected ip with cycloheximide (3 mg/kg body weight). Vitamin D3 uptake from the perfusates in cycloheximide-treated groups did not differ from controls. However, an approximately 2-fold increase of vitamin D3 retention in the perfused intestinal segments was observed after cycloheximide treatment. A 0.25-fold decrease was observed in the uptake of 1,25-dihydroxyvitamin D3 from the perfusates after cycloheximide treatment, and an approximately 2.5-fold increase in its intestinal retention was noted. An increase in the active metabolite concentration was observed in the portal venous system 75 min after initiation of perfusion, with no detectable amounts being recorded prior to the first hour. The results suggest that intracellular binding proteins may be involved in the transport of labeled vitamin D3 and labeled 1,25-dihydroxyvitamin D3 through rat enterocytes. Furthermore, vitamin D3 may have been more readily channeled through an esterification process than 1,25-dihydroxyvitamin D3 prior to their appearance in the portal venous system.

[Chondrosarcoma in Ollier's disease. Apropos of 2 cases and review of the literature]. / Les chondrosarcomes sur maladie d'Ollier. A propos de deux cas et revue de la littérature.

Ollier's disease is a rate affliction (not more than approximately 100 cases have been reported over a 30-year period) characterized by bone dysplasia in which evolution to degenerative neoplasia has been described. Diagnosis of chondrosarcoma is delicate in these cases. It is a kind of slowly evolving low grade malignant tumor. Surgery is the primary treatment course, and can lead to remission. Prognosis, depending on the number and dimension of the lesions, their localization and metastasis prevention, is usually good, but relapses are relatively frequent: 25 to 50%. In case of relapse, radiotherapy and chemotherapy were tested but their efficacy is limited. We report here two clinical cases and discuss literature data.

[Alternating chemotherapy and hyperfractionated accelerated radiotherapy in non-metastatic inflammatory breast cancer]. / Radiothérapie hyperfractionnée accélérée alternée avec une chimiothérapie dans le cancer du sein inflammatoire non métastatique.

PURPOSE: Based on encouraging results reported in alternating radiotherapy and chemotherapy in inflammatory breast carcinoma, we have tried in this study to optimize locoregional treatment with a hyperfractionated accelerated radiotherapy schedule alternating with chemotherapy. PATIENTS AND METHODS: From May 1991 to May 1995, 54 patients, previously untreated, with non-metastatic inflammatory breast cancer were entered in an alternating protocol consisting of eight courses of combined chemotherapy and two series of loco-regional hyperfractionated accelerated radiotherapy with a total dose of 66 Gy. Hyperfractionated accelerated radiotherapy was started after three courses of neoadjuvant chemotherapy (Adriamycin, Vincristine, Cyclophosphamide, Methotrexate, 5-fluoro-uracile) administered every 21 days +/- G.CSF. The first series delivered 45 Gy/three weeks to the breast, the axillary, subclavicular and internal mammary nodes, with two daily sessions of 1.5 Gy separated by an interval of eight hours; the second series consisted of a boost (21 Gy/14 fractions/10 d) alternating with another regimen of anthracycline-based-chemotherapy (a total of five cycles every three weeks). Hormonal treatment was given to all patients. RESULTS: Of the 53 patients evaluated at the end of the treatment, 44 (83%) had a complete clinical response, seven (13%) had a partial response (> 50%) and two (4%) had tumoral progression. Of the 51 patients who were locally controlled, 18 (35%) presented a locoregional recurrence (LRR); eight (15%) had to undergo a mastectomy. All the patients but two with LRR developed metastases or died of local progressive disease and 26 (50%) developed metastases. With a median follow-up of 39 months (range: 4-74 months), survival rates at three and five years were respectively, 66 and 45% for overall survival and 45 and 36% for disease-free survival. CONCLUSION: Alternating a combination of chemotherapy and hyperfractionated accelerated radiotherapy is a well-tolerated regimen which provides acceptable local control. The systemic dissemination remains the major problem of inflammatory breast carcinoma and further clinical trials using alternative drug regimens are warranted.

Endoscopic removal of an ectopic third molar obstructing the osteomeatal complex.

We report a rare case of an ectopic third molar at the level of the osteomeatal complex. A 21-year-old man came to us with a left-sided nasal obstruction of 2 years' duration. Computed tomography of the paranasal sinuses revealed that an aberrant tooth was obstructing the osteomeatal complex and bulging into the ethmoid infundibulum. Opacity of the entire left maxillary sinus indicated the presence of an associated cystic formation. A transnasal endoscopic sinus technique was employed to create a large middle meatal antrostomy and to remove the tooth as well as the cystic contents and cyst wall. Pathologic analysis revealed that the cyst was dentigerous. After recovery from surgery, the patient resumed nasal breathing. The endoscopic surgical approach used in this case caused less morbidity than do the more common methods (e.g., the Caldwell-Luc procedure) of removing ectopic teeth from the sinus.

[Carcinomatous meningitis: rare complication of bladder cancer]. / La méningite carcinomateuse: une complication rare du cancer de la vessie.

The sites of metastases of transitional cell carcinoma of the bladder are nodes, liver, lung and bone, but the meningeal infiltration is rare. Therefore, one case of meningeal carcinomatosis is reported. After cystectomy for an undifferentiated carcinoma of the bladder, the patient received adjuvant chemotherapy. Three months after treatment completion, symptoms of cerebellar ataxia occurred and gradually confusion appeared. The initial cerebra spinal fluid showed clumps of malignant cells. The patient died 15 days after the neurological symptoms occurred. The clinical diagnosis of meningeal carcinomatosis is based on neurological manifestations at more than one level of the neuraxis. Symptoms may present simply as headache or confusion. Meningeal carcinomatosis from urothelial cancer seems to show some specific features: poorly differentiated tumour and high frequency of cerebellar symptoms. Intrathecal treatment essentially has a pain-effect. Mean survival time is as short as 20 weeks. The increasing incidence of this neurological complication in urothelial cancer does not only result from an increase in patient longevity but also from possible side-effects of chemotherapy, so as localized changes in blood-brain barrier permeability induced by antineoplastic drugs. Therefore, we may wonder whether meningeal carcinomatosis might not be regarded as an iatrogenic effect.

[Epidermoid carcinoma of the head and neck: contribution of chemotherapy in case of recurrence and locally advanced disease. Review of the literature]. / Les carcinomes épidermoïdes de la tête et du cou: Place de la chimiothérapie dans les récidives et les stades localement avancés à travers une revue de la littérature.

Epidermoid carcinoma of the head and neck accounts for 10% of all cancers. At diagnosis, 60% of patients have a locally advanced disease, leading to high mortality and major functional handicaps. Chemotherapy has been shown to be active in patients presenting metastatic and/or locoregional recurrence, with 20 to 30% response rates, although no clearly established survival benefit has been demonstrated. Combining chemotherapy with surgery and/or radiotherapy has become possible with the development of new drugs and has recently led to major changes in management protocols for locally advanced epidermoid carcinoma of the head and neck. Therapeutic gain has been focalized on improving locoregional control, decreasing metastatic spread, and on the concept of an organ conservation strategy with schedules including chemotherapy as an inducing, concomitant, or alternating treatment with radiotherapy. Although many agents have demonstrated their efficacy, the role of chemotherapy in epidermoid carcinoma of the head and neck is not totally defined. The aim of treatment in metastatic and/or locoregional recurrent disease is palliative care. Regimens associating cisplatinum give a high response rate in patients previously untreated, without any real benefit in terms of survival. An evaluation of the activity of new agents with novel modes of action is currently under way. In locally advanced disease, concomitant chemotherapy with radiotherapy seems to give a minimal but real benefit as evidenced in the different meta-analyses recently published.

Phase II trial of chemotherapy with 5-fluorouracil, bleomycin, epirubicin, and cisplatin for patients with locally advanced, metastatic, or recurrent undifferentiated carcinoma of the nasopharyngeal type.

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.

Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type.

BACKGROUND: This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT). PATIENTS AND METHODS: Between July 1989 and December 1991, 44 consecutive patients (M/F 36/8; median age: 45, range 20-72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m2/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m2 epirubicin, 10 mg/m2 mitomycin, and 100 mg/m2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria. TOXICITY: Grade 3-4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3-4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles (11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3-4 mucositis occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity. RESPONSE: Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71-100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months. CONCLUSION: The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.