Results of randomised phase II studies comparing S16020 with methotrexate in patients with recurrent head and neck cancer.

BACKGROUND: The purpose of this study was to carry out two randomised phase II trials of S16020, a new olivacine derivative, tested as a single agent in patients with recurrent head and neck cancer, using methotrexate as the control arm to validate the results. PATIENTS AND METHODS: S16020 at either 80 or 100 mg/m2 was administered as a 3-h infusion every 3 weeks. Methotrexate, 40 or 50 mg/m2, was given by bolus injection, weekly for a minimum of 6 weeks. In total, 36 patients were entered in the randomised studies (25 in an initial study, 11 in a confirmatory study) of whom 24 received S16020 and 12 received methotrexate. RESULTS: A scheduled interim analysis showed one patient having a non-confirmed objective response with S16020 and three patients having a confirmed objective response with methotrexate. In the methotrexate group, there were no patients with severe non-haematological toxicity. With S16020, there was a high incidence of severe non-haematological toxicities, including asthenia, oedema of the face, oedema and pain at the tumour sites and erythematous rash; consequently, both studies were stopped. CONCLUSIONS: Both studies were stopped due to the poor anticipated benefit/risk ratio for S16020, although time to progression and overall survival time were similar in both treatment arms.

Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy.

PURPOSE: A phase II trial was performed to evaluate the efficacy, tolerance, and pharmacokinetic profiles of oral vinorelbine (Navelbine). Oral Navelbine (NVB; Pierre Fabre Médicament, Boulogne, France) was given as first-line chemotherapy for locally advanced or metastatic breast carcinoma (ABC). PATIENTS AND METHODS: Sixty-four patients were entered to receive oral NVB on a weekly basis for a total of 8 weeks unless progression or toxicity occurred. Oral NVB was given at 60 mg/m(2) weekly for the first three administrations and was increased to 80 mg/m(2) for the subsequent administrations if there was no grade 4 neutropenia or no more than one episode of grade 3 neutropenia. Patients with objective response or stable disease continued treatment up to a total of 12 weeks or more. RESULTS: Fifty-eight evaluable patients were included in our study. Four patients (6.9%) had complete responses, and 14 (24.1%) had partial responses, for an overall response rate of 31% (95% CI, 19% to 43%). Median progression-free survival was 17.4 weeks. Median overall survival is not yet reached. There were no treatment-related deaths. The main toxicity was neutropenia: grade 4 in 17.2% of the patients, and 1.8% of administrations and associated clinical serious events in 4 patients (6.2%). Grade 3 and 4 nausea and/or vomiting were noted in 3.1% and 4.6% of the patients, respectively. Only one patient developed grade 3 neuroconstipation. An analysis of Quality of Life Questionnaire C30 forms revealed no significant alteration between baseline and weeks 8 and 16 in global quality of life. CONCLUSION: Oral NVB at this schedule is an effective and well-tolerated agent in the treatment of ABC and offers a promising alternative to the intravenous route. Combination studies are ongoing.

Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck.

This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m(2)administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9-20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7-28.1 months; 95% CI: 3.9-7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B(12)supplementation.

[Cancers of the base of the tongue and hypopharynx: results of a multicenter randomized trial of chemotherapy prior to locoregional treatment]. / Cancers de la base de langue et de l'hypopharynx: résultats d'un essai multicentrique randomisé de chimiothérapie avant traitement locorégional.

The authors report the results of a multicentric randomised trial assessing the effects on survival of neoadjuvant chemotherapy with cisplatin (100 mg/m2, D1) and fluorouracil (1 g/m2, D2-4) delivered before regional treatment in patients with squamous cell carcinoma of hypopharynx and base of tongue. 133 patients were enrolled in the study, and 121 were included in the analysis, 64 in group A (regional treatment alone) and 27 in group B (chemotherapy followed by regional treatment). Despite a high objective response rate to chemotherapy (primary tumour: 85%, 24% complete; nodes: 63%), overall survival was not significantly higher in group B than in group A.

[Diabetes insipidus caused by metastasis to the hypothalamo-hypophyseal axis. Apropos of 4 cases]. / Diabète insipide par métastase de l'axe hypothalamo-hypophysaire. A propos de 4 cas.

This study concerns the cases of 4 patients with polyuria and polydipsia syndrome as part of a known evolutive neoplasia. MRI demonstrated an intra- and supersellar tumoral process developed from the pituitary stalk and the posterior pituitary lobe suggesting metastasis.

Sequential chemotherapy and radiotherapy for patients with squamous cell carcinoma of the esophagus.

BACKGROUND: Despite surgical improvements the prognosis of patients with squamous cell carcinoma (SCC) of the esophagus remains poor, with a 5-year survival rate of less than 20%. Most patients do not undergo surgery with curative intent. The aim of this study was to assess the toxicity and efficacy of sequential chemoradiotherapy. METHODS: Between May 1986 and June 1991, 50 patients with nonmetastatic SCC of the esophagus were included in this study. Three patients had recurrence after surgery, 8 patients were classified Stage I disease, 24 Stage II, 5 Stage III, and 10 Stage VI. Treatment consisted of cisplatin (100 mg/m2 on Days 1 and 29), 5-fluorouracil (5-FU) (600 mg/m2 on Days 2-9 and Days 30-33) and 30 Gy of radiotherapy (2 Gy x 15 on Days 8-26 and 30 Gy on Days 36-54). RESULTS: Thirty-seven patients (74%) received the whole treatment course; treatment was modified for 8 patients because of Grades III and IV hematologic, digestive, or renal toxicity. Five patients did not complete treatment because of disease progression or death. Median survival was 13 months; 1- and 2- year survival rates were 63% (49-75) and 36% (25-50), respectively. No late treatment complications were observed (in the 11 survivors after 2 years. CONCLUSIONS: Sequential chemoradiotherapy of SCC of the esophagus was well tolerated with acceptable acute morbidity and resulted in local control and survival results at least equivalent to those in trials of neoadjuvant chemoradiotherapy plus surgery.

A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus.

BACKGROUND: Despite well-established surgical approaches, the prognosis for patients with squamous cell carcinoma of the esophagus remains dismal. To assess the benefit of adjuvant chemotherapy and radiation therapy (CRT), a randomized trial with and without sequential preoperative CRT was undertaken; CRT combined 20 Gy and two courses of 5-FU and cisplatin. METHODS: Patients were included on the basis of the following criteria: squamous cell carcinoma of the esophagus, younger than 70 years of age, World Health Organization status below 2, estimated survival time greater than 3 months, and no previous treatment for the cancer. Patients were not included if they had experienced a loss in body weight greater than 15% or had tracheoesophageal fistula, metastases, or uncontrollable infection. RESULTS: Eighty-six patients thus fulfilled the criteria for inclusion (41 CRT, 45 non-CRT). The groups were well-matched for age, sex, tumor location, size, and grade. Operative mortality was 8.5% and 7%, respectively, for each group with a 27-day hospital stay for both groups. Long-term survival was not significantly different, with 47% of both groups alive at 1 year. CONCLUSIONS: The authors concluded that this neoadjuvant treatment did not change operative mortality or survival time for patients with squamous cell carcinoma of the esophagus.

[Primary seropapillary peritoneal carcinoma. 16 case reports. Review of the literature]. / Carcinome séropapillaire primitif du péritoine. A propos de 16 observations. Revue de la littérature.

OBJECTIVE: Review of primary seropapillary carcinoma of the peritoneum. TYPE OF STUDY: Retrospective. PLACE: Department of Gynaecology and Oncology, University Hospital, Rennes. SUBJECT: 16 patients who underwent chemotherapy and surgery. RESULTS: Mean age at onset was 62 years with a late clinical diagnosis at an advanced stage. Macroscopically, peritoneal miliary was often associated with a predominant tumoural formation on the epiploon. Treatment included surgical exeresis with endoxan-cisplatin chemotherapy. The prognosis was equivalent to ovarian tumours at similar stages. CONCLUSION: Primary seropapillary carcinosis of the peritoneum is a separate group of peritoneal carcinosis distinguishable from peritoneal mesotheliomas and which have a prognosis similar to ovarian tumours. These tumours should be classed as part of the large group of mullerian tumours.

Postmenopausal patients with node-positive resectable breast cancer. Tamoxifen vs FEC 50 (6 cycles) vs FEC 50 (6 cycles) plus tamoxifen vs control--preliminary results of a 4-arm randomised trial. The French Adjuvant Study Group.

In 1986 the true benefit of adjuvant medical treatment in postmenopausal patients with pathological node-positive breast adenocarcinoma was still controversial. The French Adjuvant Study Group (FASG) initiated a randomised trial to elucidate the respective roles of adjuvant chemo-and/or hormonotherapy in this group of patients. Of the 776 patients who have been included between 1986 and 1990, 741 were fully eligible for evaluation. Inclusion criteria were postmenopausal patients aged between 50 and 70 years with adenocarcinoma of the breast, positive pathological nodes and no distant metastasis. Patients were randomised to 1 of 4 treatment arms: Group A (n = 192) received tamoxifen 30 mg/day orally for 3 years; Group B (n = 183) received FEC 50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2 plus cyclophosphamide 500 mg/m2) for 6 cycles; Group C (n = 182) received tamoxifen 30 mg/day orally for 3 years plus FEC 50 for 6 cycles; Group D (n = 184) received no medical adjuvant treatment. Surgery was either modified radical mastectomy (n = 363) or tumorectomy (n = 378), and postoperative irradiation was given to all patients. All major prognostic factors were well balanced between the 4 patient groups. Toxicity was evaluated in 348 patients in Groups B and C who received a total of 1983 chemotherapy cycles. Median epirubicin dose intensity (mg/m2/week) was 15.8 in Group B and 15.7 in Group C. Grade 3 to 4 neutropenia was observed in 4.7% of cycles for Group B and 3.7% for Group C. Grade 3 to 4 nausea/vomiting were seen in 18% of treatment cycles in Group B and 15% in Group C.(ABSTRACT TRUNCATED AT 250 WORDS)

Unusual combination of Cis platinum and radiotherapy followed by a three fractions per day irradiation in splitcourse: a phase I-II study in brain glioma patients.

An unusual protocol based on a preliminary clinical study on cylindromas metastasized to the lung was proposed to brain glioma patients: Day 2 100 mg/m2 i.v. Cis platinum (Cis PII) followed at days 3 and 5 by 6 Gy irradiation (RT) in two fractions and three days. Five cycles were scheduled at 21 days interval. On disease progression a three fractions per day radiotherapy regimen (3 FRT) in split-course (two series of 22.50 Gy in 15 fractions and five days separated by a two weeks period of rest) was then delivered to the patients. All patients had a measurable mass on the CT scan. 19 were entered into the study: 13 as first line therapy (group A) and six for salvage treatment (group B). Tolerance was globally good. Eight patients were considered responders at the end of five cycles of Cis PII-RT. They were all group A patients. Median symptom-free interval was six months for the whole population. Survival was twelve months. The 3 FRT was well tolerated but does not seem to have improved the therapeutic gain of the chemoradiotherapy combination. The present study concerns patients whose prognosis was poor on inclusion: surgery inadvisable or unsatisfactory and diagnosis mainly based on biopsy only. The number and the duration of responses justify further study into Cis PII as first line therapy as either an effective cytotoxic drug or a potential radio enhancer.

[Excision of an intracardiac metastasis under chemotherapy]. / Exérèse d'une métastase intra-cardiaque sous chimiothérapie.

An intracardiac malignant lesion was found in a 28-year old male patient following orchidectomy for an advanced germinal tumour of the testicle. Although the patient is under chemotherapy, the neoplastic thrombus will be removed by surgery. Heart metastases are uncommon. When they do occur, they are usually secondary to locoregional extension and limited to the pericardium or myocardium. Endocardial or intracavitary lesions are rare, but can, in certain cases, be removed by surgery.

Effect of HECNU in malignant supratentorial gliomas--a phase II study.

Forty adults with recurring brain gliomas were treated with HECNU 130 mg/m2, given i.v. every 5 to 6 weeks (mean 5.4) and corticosteroids. According to the response to treatment, patients were divided in 3 groups: 1. Group 1 included 8 pts (20%) with objective remission, defined as a clear-cut clinical improvement persisting at least 4 weeks after the complete discontinuation of corticosteroids. 2. Group 2 included 14 patients (35%) who improved or remained stable yet stayed corticosteroid-dependent. 3. The 18 patients (45%) of group 3 failed to respond. There was a fair correlation between clinical and radiological response. Thus sequential CT-scans showed a 50 to 100% tumour reduction in all patients of group 1, and in 5 of group 2. CT-scans remained unchanged in 8 patients of group 2 and in one of group 3, and showed tumour progression in 10 patients of group 3. Drug toxicity appeared mild, reversible and was not cumulative. The better tolerance of HECNU could represent a real advantage of this drug over the commonly used nitrosourea derivatives such as BCNU and CCNU.

[Immunoscintigraphy, an aid to the oncologist--the Rennes experience in using anti-CEA, anti-CA 19.9 monoclonal antibodies and radiolabelled OC-125]. / L'immunoscintigraphie, une aide pour le cancérologue--expérience rennaise de l'utilisation des anticorps monoclonaux anti-ACE, anti-CA 19.9 et OC-125 radiomarqués.

Immunoscintigraphy is steadily asserting itself as a valuable method in the localization of malignant tumours, alongside other imaging techniques. A monoclonal antibody specific to one or several tumour cell lines is used. The antibody is labelled with a gamma emitter radioisotope and so that it can be detected in vivo. We have evaluated three monoclonal antibodies (F(ab')2 fragments): a mixture of anti-CEA and anti-19.9 antibodies in the investigation of colorectal carcinoma and the antibody OC-125 in ovarian cancer. In our experience, it appears that pelvic recurrence is the best indication for immunoscintigraphy. Antibodies can apparently be safely used in man. We noted no side-effect following the injection of anti-CEA, anti 19.9 and OC-125.

[Similar evolution, with cerebral metastases, of testicular cancers in 2 non-twin brothers]. / Evolution similaire, avec métastases cérébrales, de cancers testiculaires chez deux frères non jumeaux.

The authors describe two cases of germinal carcinoma of the testis. The two patients were brothers, but not twins. The evolution of the disease was the same in both cases, with cerebral metastases. The etiology was not discovered but the localization of the metastases in the brain would seem due to the fact the antimitotic drugs used in therapy failed to cross the brain blood barrier.

[Value of aspiration cytology for the evaluation of breast cancer recurrence]. / Intérêt de la ponction cytologique pour l'évaluation des recidives carcinomateuses du sein.

The authors studied at the "Centre Anticancéreux de Rennes" the value of fine needle aspiration cytology in the valuation of recurrences in breast cancers. The cytologic procedures were made on breast scars. The cytologic investigation interested 32 cases of carcinoma recurrences. The high rate of correct cytology diagnosis and the very low of wrong results prove the value and interest of the fine needle aspiration cytology for recurrences in breast cancers.

[Malignant chemodectoma of the intrapetrous facial nerve]. / Chémodectome malin du nerf facial intrapétreux.

A 30 year old man presented with a tumor of the intrapetrous portion of the facial nerve, found to be a malignant chemodectoma on investigation. Possible relations with tumors of the APUD system, as well as pathogenic and therapeutic aspects are discussed.