Neuronal density and proportion of interneurons in the associative, sensorimotor and limbic human striatum.

The striatum (caudate nucleus, putamen and nucleus accumbens) is the main input structure of the basal ganglia. It receives cortical projections from the vast majority of the cortex, as well as from other subcortical structures such as the thalamus and amygdala. Its role in planning, preparation and execution of voluntary movements is known to be fine-tuned by the interaction between projection neurons and interneurons. Since the 1990s, it has been accepted that the proportion of interneurons increases phylogenetically, being about 5% in rodents and 26% in humans. However, these data have not been confirmed with unbiased techniques, such as stereology. In the present report, we have divided the human striatum into functional territories (associative, sensorimotor and limbic) and we have quantified the numerical density of all striatal neurons (using Nissl staining) in each area. Taking into account our past research on the estimation of striatal interneurons, we have calculated the proportion of interneurons in each territory. This value was on average 17.1% for the whole striatum, although interneurons were more abundant in the associative (21.9%) than in the sensorimotor (12.8%) and limbic (11.1%) aspects. Therefore, we demonstrate with unbiased stereology that the overall proportion of striatal interneurons is slightly lower than that reported in previous studies, and that it varies in the functional territories of this structure.

[Laryngeal Preservation with Induction Chemotherapy. Experience of two GETTEC Centers, Between 1985 and 1995]. / Préservation laryngée par chimiothérapie d'induction.

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.

Early locoregional high-dose radiotherapy is associated with long-term disease control in localized primary angiocentric lymphoma of the nose and nasopharynx.

Nasal NK/T cell is a rare form of usually localized non-Hodgkin's lymphoma (NHL) which generally carries a poor prognosis when treated with conventional NHL chemotherapy protocols. We reviewed 20 consecutive localized stage I/II nasal NK/T cell lymphomas treated at our institution over a 29 year period. Median age was 44 (range 23-71). Front-line therapy was generally radiotherapy alone (35-70 Gy) before 1980 and combination chemotherapy after 1980. Six patients were treated with first-line radiotherapy and they achieved complete remission (CR). Two subsequently received combination chemotherapy. Five of those patients remained in complete remission, after 97+ to 277+ months. Twelve patients were treated with first-line chemotherapy including CHOP or CHOP-like regimen in seven cases, and COP in five cases. Only three of them achieved CR, five had partial response and four had progressive disease. Five of the seven patients treated with CHOP did not achieve complete remission. The nine patients who failed to achieve CR with chemotherapy subsequently received salvage radiotherapy but only two of them obtained CR. Finally, two patients were treated with alternated chemotherapy and radiotherapy and achieved CR, which persisted after 14+ and 26+ months. Median survival was not reached in patients who received front-line radiotherapy, and was 35 months in patients who received front-line chemotherapy. These findings confirm that chemotherapy gives a low complete remission rate in localized nasal NK/T cell lymphoma. By contrast, first-line radiotherapy seems to give favorable results, whereas its results are poorer when administered after resistance to chemotherapy. Whether the use of chemotherapy after radiotherapy, or alternated chemotherapy-radiotherapy regimens give better clinical results than radiotherapy alone will have to be evaluated prospectively in this type of NHL.

Full dose reirradiation combined with chemotherapy after salvage surgery in head and neck carcinoma.

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.

Result of two randomized trials comparing nolatrexed (Thymitaq) versus methotrexate in patients with recurrent head and neck cancer.

We report on two randomized trials performed in the USA and Europe, which compared methotrexate and nolatrexed as treatment for patients with recurrent head and neck cancer. Eligibility criteria included: histologically confirmed squamous-cell carcinoma, measurable disease, adequate hematological, renal and hepatic functions, failure of a first-line chemotherapy, and informed consent. Methotrexate 40 mg/m2 was weekly given by short infusion, and nolatrexed 725 mg/m2 per day was administered as a five-day continuous infusion, every three weeks. A total of 139 patients (63 in the USA. 76 in Europe) were randomized based on a ratio of 2/1: 93 and 46 received nolatrexed and methotrexate, respectively. Patient characteristics included 115 males and 24 females; median age 60 years. In the nolatrexed arm, the following grade 3-4 toxicities occurred: neutropenia (29.9%) with 3.1% of febrile neutropenia, mucositis (33.3%), and vomiting (10.3%). In the MTX arm, the grade 3-4 toxicities were neutropenia (7.1%) and mucositis (6.9%). There was no difference in activity between the nolatrexed and the methotrexate treatment: 3.3% and 10.8% of objective responses, 1.9 versus 1.5 months of disease-free progression and 3.5 versus 3.7 months of overall survival, respectively. Nolatrexed has demonstrated a similar activity to methotrexate.

Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer.

BACKGROUND: Despite more than 70 randomised trials, the effect of chemotherapy on non-metastatic head and neck squamous-cell carcinoma remains uncertain. We did three meta-analyses of the impact of survival on chemotherapy added to locoregional treatment. METHODS: We updated data on all patients in randomised trials between 1965 and 1993. We included patients with carcinoma of the oropharynx, oral cavity, larynx, or hypopharynx. FINDINGS: The main meta-analysis of 63 trials (10,741 patients) of locoregional treatment with or without chemotherapy yielded a pooled hazard ratio of death of 0.90 (95% CI 0.85-0.94, p<0.0001), corresponding to an absolute survival benefit of 4% at 2 and 5 years in favour of chemotherapy. There was no significant benefit associated with adjuvant or neoadjuvant chemotherapy. Chemotherapy given concomitantly to radiotherapy gave significant benefits, but heterogeneity of the results prohibits firm conclusions. Meta-analysis of six trials (861 patients) comparing neoadjuvant chemotherapy plus radiotherapy with concomitant or alternating radiochemotherapy yielded a hazard ratio of 0.91 (0.79-1.06) in favour of concomitant or alternating radiochemotherapy. Three larynx-preservation trials (602 patients) compared radical surgery plus radiotherapy with neoadjuvant chemotherapy plus radiotherapy in responders or radical surgery and radiotherapy in non-responders. The hazard ratio of death in the chemotherapy arm as compared with the control arm was 1.19 (0.97-1.46). INTERPRETATION: Because the main meta-analysis showed only a small significant survival benefit in favour of chemotherapy, the routine use of chemotherapy is debatable. For larynx preservation, the non-significant negative effect of chemotherapy in the organ-preservation strategy indicates that this procedure must remain investigational.

Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Groupe d'Etude des Tumeurs de la Tête et du Cou (GETTEC).

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.

A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck.

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m(-2) by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1-9) per patient. The median cumulative dose was 449 mg m(-2). Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1-50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4-52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h(-1) m(-2) and an area under the curve of 6.00 microg ml(-1) h(-1) was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance.

Percutaneous gastrostomy with fluoroscopic guidance: single-center experience in 500 consecutive cancer patients.

PURPOSE: To evaluate the feasibility, complications, adequacy of feeding support, and tolerability of fluoroscopically guided gastrostomy in cancer patients. MATERIALS AND METHODS: Five hundred cancer patients were referred for fluoroscopically guided gastrostomy, among whom percutaneous endoscopic gastrostomy was contraindicated or had been unsuccessful in approximately one-fourth. Five hundred eight fluoroscopically guided gastrostomies with T-fastener gastropexy were performed in 496 patients. The procedure was unsuccessful in four patients, and 12 patients needed a second gastrostomy. RESULTS: Fluoroscopically guided gastrostomy was feasible in 99% of patients. During the first 30 postprocedure days, there were seven major complications (1.4%): cardiac failure (n = 1), hemorrhage (n = 1), and peritonitis (n = 5); one patient died of peritonitis. No major complications occurred after the 30th postprocedure day. There were 27 minor complications (5.4%) during the first 30 postprocedure days and 88 (17.6%) thereafter. Long-term minor complications mainly involved the disturbances and nearly always resolved once the tube was exchanged. Such exchanges were easily performed under fluoroscopic guidance except in two patients, who required repeat fluoroscopically guided gastrostomy. CONCLUSION: Fluoroscopically guided gastrostomy is highly feasible and safe and provides adequate feeding support, even when percutaneous endoscopic gastrostomy is impossible. Long-term complications, which are mainly tube disturbances, are easily treated.

Full-dose reirradiation for unresectable head and neck carcinoma: experience at the Gustave-Roussy Institute in a series of 169 patients.

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.

Combined transfacial and neurosurgical approach to malignant tumours of the ethmoid sinus.

In order to understand the risks and benefits of a combined transfacial and neurosurgical procedure for neoplasms of the ethmoid sinus, we reviewed all patients who underwent this surgical approach in our department between 1986 and 1994. The study included 41 patients. Pathological diagnoses included adenocarcinoma (31 patients), squamous cell carcinoma (three patients), aesthesioneuroblastoma (three patients), other (four patients). The overall morbidity rate was 39 per cent, and the post-operative mortality rate was 2.5 per cent. Complications were statistically more likely in patients with bone skull base reconstruction. The main carcinologic failures were local recurrences (24 per cent) and metastases (22 per cent). The one-year, three-year and five-year Kaplan Meir survival rates were respectively 84 per cent, 53 per cent and 36 per cent. In conclusion, the mortality and morbidity were acceptable, especially when no bone skull base reconstruction was performed. Better local control justifies a combined procedure with post-operative radiotherapy when tumours involve or reach the skull base.

Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy.

Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents by administering the drug in combination with short intense electric pulses. ECT is effective because electric pulses permeabilize tumour cell membranes and allow non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on cutaneous and subcutaneous tumours. This article summarizes results obtained in independent clinical trials performed by five cancer centres. A total of 291 cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated in 50 patients. Short and intense electric pulses were applied to tumours percutaneously after intravenous or intratumour administration of bleomycin. The tumours were measured and the response to the treatment evaluated 30 days after the treatment. Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed. ECT was shown to be an effective local treatment. ECT was effective regardless of the histological type of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous and subcutaneous tumours in patients with minimal adverse side-effects and with a high response rate.

Red blood cell glutathione levels before and during treatment with neoadjuvant chemotherapy cisplatin/5-fluorouracil in patients with head and neck squamous cell carcinoma.

The purpose of this study was to find out whether the glutathione (GSH), in red blood cells could predict the response to neoadjuvant chemotherapy cisplatin/5-fluorouracil (CDDP/5-FU) in patients with head and neck squamous cell carcinoma (HNSCC). Three courses of induction chemotherapy with CDDP/5-FU were administered and followed by surgery and radiotherapy or radiotherapy alone, in 51 patients with HNSCC. GSH was measured by spectrophotometry in red blood cell before any treatment (Sample 1: S1), after each course of chemotherapy (S2, S3, S4). Our results showed that GSH was the same at diagnosis in patients with complete or partial response (OR) compared to those with stable or progressive disease (NR). With regard to evolution of the GSH during the 3 courses of CT a significant difference was found between courses (S2: 5.06 +/- 0.35 vs S4 = 3.61 +/- 0.4 mumol/g haemoglobin, p < 0.05). When we separated our patients into OR and NR, a significant difference was found over the 3 courses of chemotherapy for GSH content. Non responder patients showed decreased GSH content at the end of the treatment, (S2: 5 +/- 0.5 vs S4: 2.2 +/- 0.4 mumol/g haemoglobin, p < 0.05) while OR were stable. In conclusion, red blood cell GSH seems to have no early predictive value for chemoresponse to neoadjuvant chemotherapy CDDP/5-FU in HNSCC.

[Isolated mandibular metastasis of cancer of the thyroid. Mandibulectomy and reconstruction using a free vascularized peroneal graft]. / Métastase mandibulaire isolée d'un cancer de la thyroïde. Mandibulectomie et reconstruction par un transplant libre de péroné vascularisé.

Isolated mandibular metastasis from a thyroid cancer is exceptional. In our observation, it was revealed 13 years after the thyroid cancer (papillo-vesicular carcinoma which was treated with total thyroidectomy, nodes resection and I 131). Treatment included interruptive mandibulectomy and reconstruction with a free composed vascularized fibular transplant. Follow-up was uneventful. Functional and morphological results were excellent. Isolated cases are reported in the literature. Surgical resection must be achieved. The originality of our observation is the mandibular reconstruction with a free vascularized fibular transplant.

Erdheim-Chester disease with prominent pulmonary involvement associated with eosinophilic granuloma of mandibular bone.

We report a patient with eosinophilic granuloma localized to the left mandible who was subsequently shown to have Erdheim-Chester disease involving the lower extremities, omentum and lung. The diagnosis of eosinophilic granuloma was based on the presence of typical CD1a+ Langerhans' cell granulomas in a biopsy of mandible. The diagnosis of Erdheim-Chester disease was established on the basis of the pattern of radioisotopic uptake by long bones, seen on a technetium bone scan, and the presence of characteristic histopathological features in biopsies of lung and peritoneum. The pathological findings in lung were compatible with the abnormalities observed by tomodensitometry, but strikingly different from those seen in Langerhans' cell granulomatosis. The differences in the histological features of pulmonary involvement seen in the two diseases, and the possible relationship between Langerhans' cell granulomatosis and Erdheim-Chester disease, are discussed.

[Isolated mandibular metastases. Therapeutic strategy. Apropos of 7 cases]. / Les métastases mandibulaires isolées. Stratégie thérapeutique. A propos de 7 cas.

Among the mandibular tumours, the secondary malignant tumours are uncommon. We relate 7 cases observed between 1977 and 1995. Two cases have revealed the original cancer (rectum, prostate). The five other cases were discovered during the evolution of the original cancer (colon, lung, kidney, thyroid, breast). These 7 mandibular metastases were isolated. The treatment included a mandibular resection in 6 cases. In one of these cases, the reconstruction was performed with a free vascularized fibular transplant with success. Among the seven cases, two patients are alive, at the present time, with a mean follow-up of 3 years. This justifies a curative treatment.

Neoadjuvant chemotherapy with cisplatin-vindesine-5-fluorouracil and folinic acid for locally advanced head and neck carcinoma.

The aim of this study was to establish the feasibility, evaluate the response rate, and assess the impact on local control and survival in locally advanced (bulky nodal) squamous cell carcinoma of the head and neck (SCCHN) patients treated with neoadjuvant chemotherapy consisting of cisplatin followed by continuous infusion of vindesine and fluorouracil with intermittent i.v. folinic acid. Eligibility criteria included histologically proven SCCHN, previously untreated locally advanced stage III-IV with measurable or evaluable disease, no distant metastases, an Eastern Cooperative Oncology Group (ECOG) performance status of less than 2, patient age of at least 18 years, and adequate bone marrow, hepatic, and renal functions. The protocol consisted of three cycles (day 1, day 21, day 42) of Cisplatin (CDDP) 100 mg/m2/day i.v. on day 1 immediately followed by 4 days (96 h) of continuous infusion of vindesine 0.8 mg/m2/day and 5-fluorouracil (5-FU) 600-700 mg/m2/day with folinic acid 150 mg/m2 i.v. every 6 h x 16 doses before locoregional treatment with radiotherapy preceded by radical surgery when appropriate. Twenty-nine patients were enrolled in this study, and 28 were evaluable for activity; an objective response rate of 55% (four complete responses, 12 partial responses) was achieved. Leukopenia and mucositis were the most frequent and severe toxicities. The addition of vindesine did not improve the activity of the CDDP-FU-folinic acid combination, but this may be partly because of the particularly poor prognosis of the present patient population, with 75% of stage IV bulky nodal disease (N2c-N3).

[Predictive value of the hemogram for myelotoxicity induced by the association of carboplatin-fluorouracil on the 4th day of the therapeutic regimen]. / Valeur prédictive de l'hémogramme du 4e jour pour la myélotoxicité induite par l'association carboplatine-5-fluorouracile.

The aim of this study was to determine the value of haematological counts at the 4th day of a chemotherapy cycle, in order to foresee neutro and/or thrombocytopenia during the same chemotherapy cycle. One hundred and ten cycles of chemotherapeutic regimens with carboplatin (400 mg/m2, dl) and 5-fluorouracile (1 g/m2/d, by iv continuous infusion for 96 hours) every 3 weeks, were analyzed for 42 patients with locally advanced but non metastatic squamous cell carcinoma of head and neck, without prior chemotherapy. Lymphocyte counts were significantly decreased at the 4th day but normalized at the 8th day (P < 10(-6)). Decreases of lymphocyte and neutrophil counts at the 4th day were significantly correlated to grade > 2 neutropenia. The positive predictive value of lymphocyte or neutrophil counts is about 50% for some cut-off values but not high enough, with the schedule of chemotherapy in our study, to justify the systematic prophylactic therapy with haematopoietic growth factors.

Phase I-II trial of recombinant interferon alpha-2b with cisplatin and 5-fluorouracil in recurrent and/or metastatic carcinoma of head and neck.

The aims of this study were to establish the feasibility and toxicity of the biochemical modulation of the cisplatin (CDDP)-5FU combination by interferon alpha-2b (INF), and to assess its therapeutic efficacy in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). The mandatory eligibility criteria included histologically proven SCCHN; a performance status <2; adequate bone marrow, hepatic, renal, and cardiac functions; and measurable and/or evaluable disease. The protocol was CDDP, 100 mg/m2 i.v. day 1; 5-FU, 1,000 mg/m2 in a c.i.v. infusion over 96 h; and INF 3.10(6) U/day s.c., begun 2 h before cisplatinum for 5 consecutive days, repeated every 3 weeks. Twenty patients were included and received 76 cycles (median number cycles/patient = three). Eighteen patients were evaluable for activity with an overall response rate (RR) of 30% [2 complete responses (CR) + 4 partial responses (PR)], which was 55% (5/9) in previously untreated and 9% (1/11) in previously treated patients. Myelosuppression (50%), mucositis (40%), loss of electrolytes (15%), and asthenia (20%) were the most frequent severe toxic effects. Notwithstanding, the protocol was feasible and well tolerated in this overall population with a poor prognosis. Median duration of response was 8 months, and median survival for the overall population was 8.5 months. This schedule is the test arm of an ongoing international multicentric phase III trial versus standard CDDP-5FU in the same SCCHN population.

Intensive concomitant chemoradiotherapy in locally advanced unresectable squamous cell carcinoma of the head and neck: a phase II study of radiotherapy with cisplatin and 7-week continuous infusional fluorouracil.

PURPOSE: To evaluate an intensive concomitant chemoradiotherapy protocol of conventional radiotherapy with intermittent cisplatin (CDDP) and continuous-infusion fluorouracil (5-FU) in unresectable, locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Fifty-seven patients with unresectable stage IV MO disease (International Union Against Cancer [UICC]/American Joint Committee on Cancer [AJCC], 1987) received radiotherapy 70 Gy followed by CDDP 80 mg/m2 and 5-FU 300 mg/m2/d. Response was assessed 2 months after treatment completion. RESULTS: Thirty patients (52%) received the full treatment schedule; 53 (93%) received full-dose radiotherapy, while 48 (84%) were given at least 75% of the planned chemotherapy doses. Severe mucositis (World Health Organization [WHO]) grade 3 to 4 was the limiting toxicity and was seen in 79% of patients. The median time for mucositis resolution was 8 weeks. Other toxicities were generally manageable, but there were four treatment related deaths (7%). Fifty patients were assessable for activity, with an overall response rate of 70% (95% confidence interval [CI], 58% to 82%). Complete response (CR) and partial response (PR) rates were 42% and 28%, respectively. CONCLUSION: This simultaneous combined-modality regimen was feasible at the cost of severe mucosal toxicity, which required hospitalization with nutritional, parenteral, and hydroelectrolytic support. The high response rate achieved (70%) did not translate into improved survival, probably due to patient eligibility. The likelihood of cure of this high-tumoral-volume patient population remains low (approximately 10%), despite the association of two therapeutic modalities at full standard therapeutic intensity.