The effect of tirapazamine (SR-4233) alone or combined with chemotherapeutic agents on xenografted human tumours.

Recent data have shown that the in vitro and in vivo cytotoxicity of bioreductive drugs could be significantly increased when combined with chemotherapy drugs such as cisplatinum, depending on the timing of administration. The aim of this study was to define the toxicity (animal lethality) and the activity (growth delay assay, excision assay) of a bioreductive drug, tirapazamine, alone and combined with chemotherapy agents (5-FU, VP16, bleo, DTIC and c-DDP) on nude mice bearing xenografted human tumours: a rectal carcinoma (HRT18) and a melanoma (Na11+). Animal lethality was markedly increased when tirapazamine at the lethal dose 10% was combined with the other drugs.

Endoluminal high-dose-rate brachytherapy with a palliative aim in esophageal cancer: preliminary results at the Institut Gustave Roussy.

Ten patients with advanced esophageal carcinoma were treated with endoluminal high-dose-rate brachytherapy at the Institut Gustave Roussy. Eight of them had recurrences after external beam radiotherapy. They were treated with a high-dose rate iridium-192 source.

Melanoma arising de novo in childhood: experience of the Gustave-Roussy Institute.

Between January 1956 and December 1990, 17 patients younger than 17 years with available pathological screens of de novo cutaneous melanoma, and with no other risk factors (xeroderma pigmentosum, giant congenital naevi, congenital melanoma or a proven family history of dysplastic naevus syndrome) were seen at the Gustave-Roussy Institute. The median age was 9 years and 9 months (range 2 years and 3 months-16 years and 9 months). The primary disease was located in the lower extremities in 10 cases, the trunk in five cases, and the upper extremities or head and neck in one case.

Does tirapazamine (SR-4233) have any cytotoxic or sensitizing effect on three human tumour cell lines at clinically relevant partial oxygen pressure?

Solid human tumours contain areas with low oxygen tension (pO2). For bioreductive drugs it is important to define the cytotoxic effect according to drug concentration and to clinically relevant pO2. In this study, the pO2 dependence of the survival of three human cell lines (HRT 18, Na11 +, and MEWO), exposed to tirapazamine (SR-4233) alone or combined with ionizing radiation, was studied in vitro.

The role of low dose rate brachytherapy in the treatment of cervix carcinoma. Experience of the Gustave-Roussy Institute on 1245 patients.

From 1974 to 1992, 1245 patients with cervix carcinoma were treated at the Institut Gustave-Roussy using several treatment protocols all of which included LDR brachytherapy. We present and discuss the results of our experience.

Surgical salvage treatment of T1/T2 glottic carcinoma after failure of radiotherapy.

Purpose: To evaluate the use of conservative surgical salvage techniques (eg, vertical partial laryngectomy and subtotal laryngectomy with cricohyoidopexy) versus total laryngectomy for radiotherapeutic failure of early glottic cancer by retrospective review of medical records.

Patients And Methods: Of 950 previously untreated endolaryngeal carcinomas managed at the Gustave-Roussy Institute in France between 1975 and 1984, 259 of 344 early glottic cancers (T1, N0 and T2, N0) received radiation therapy. Local failure rates were 14% in T1a cancers, 16% in T1b cancers, and 36% in T2 cancers with normal vocal-cord mobility.

Sarcomas of nasal cavity and paranasal sinuses: chondrosarcoma, osteosarcoma and fibrosarcoma.

Forty-two patients were treated for sarcoma of the nasal cavity and paranasal sinuses at the Institut Gustave Roussy, Paris, between 1960 and 1993. Twelve patients had chondrosarcoma (CS), 14 had osteosarcoma (OS) and 16 had fibrosarcoma (FS). Ten patients had grade I, six grade II and 26 grade III tumours.

[Cervical cancer in the young woman].

Uterine cervix carcinoma is considered by some authors to carry a poor prognosis in young patients (< 35 years of age). From 10 years, many series have been published with divergent conclusions. However, a group of patients with poor prognosis could be individualized; age < 30 years, locally aggressive tumour, poorly differentiated, nodal involvement, amplification of c-Myc proto-oncogene.

Accelerated radiation therapy in the treatment of very advanced and inoperable head and neck cancers.

Purpose: A Phase II trial testing a continuous and accelerated regimen of radiotherapy in very advanced head and neck cancers.

Methods And Materials: From 1988 to 1990, 47 patients with very advanced and inoperable tumors (38/47 T4) of the oral cavity and the oropharynx were submitted to a continuous and accelerated regimen of hyperfractionated radiation therapy: three daily fractions of 0.9 Gy were delivered 5 days-a-week, up to the 70 Gy total dose, reducing the overall treatment time to 5.

[Immediate effect of radiation on normal tissue].

The acute effects of radiations on normal tissues are linked to known parameters. These parameters are the nature and function of the irradiated organ, and the technical characteristics of the treatment (treated volume, beam energy, fractionation). The intensity and time course of the clinical reactions depend on these parameters.

Male breast carcinoma: a single centre report of clinical parameters.

A total of 68 men (mean age 66.2 years) were treated for a primary carcinoma of the breast at Mount Vernon Hospital between January 1968 and June 1988. The mean duration of the symptoms before diagnosis was 13.

[Brachytherapy in cancer of the urethra].

Carcinomas of the male and female urethra are serious cancers because they frequently present late with lymph node involvement. Brachytherapy plays a significant role, often associated with external beam irradiation and surgery, in the conservative management of these tumors. This radiation treatment uses a catheter or a vaginal mould applicator for intraluminal/intracavity brachytherapy, and hypodermic needles or guide gutters for the interstitial portion.

[Brachytherapy in cancer of the penis].

Brachytherapy can play an essential role in the conservative treatment of penile cancer limited to the glans. This treatment is usually performed using hypodermic needles with templates which are subsequently loaded with iridium wires. Various studies, particularly French reports, show a local control rate of 80%, penis preservation in 75% of cases and a specific survival rate of 60%.

[Brachytherapy in prostatic adenocarcinoma].

Brachytherapy can represent the exclusive treatment of localized prostatic adenocarcinoma. Several techniques have been described: permanent implantations with 125-iodine or 198-gold seeds or temporary implantations with 192-iridium. These implantations are performed either via a retropubic approach, often combined with pelvic lymphadenectomy, or via a transperineal approach, with or without ultrasound guidance.

[Brachytherapy of the bladder].

Brachytherapy has a key role to play in the treatment of bladder carcinoma. It is generally combined with partial bladder resection for limited tumours (T1-2, N0, M0). Results obtained in Holland and France have shown 80% local control with limited morbidity.

Tumor oxygenation after 1) carbogen and/or perflubron emulsion administration in tumor xenografts 2) carbogen administration in patients.

This study examines the changes in tumor pO2 distribution assessed by polarography (KIMOC 6650, Eppendorf) in 1) two human tumor xenografts after carbogen inhalation with or without a perflubron (perfluorooctylbromide) emulsion (Oxygent, Alliance Pharmaceutical corp.) and in 2) human head and neck carcinomas after carbogen inhalation. Mice bearing HRT18 or NA11+ tumors were restrained and their body temperature was kept constant.

Nicotinamide and carbogen: major effect on the radiosensitivity of EMT6 and HRT18 tumours.

The effect of nicotinamide and/or carbogen breathing on the response of EMT6 and HRT18 tumours, irradiated in vivo, was evaluated using an in vitro colony assay. In the single dose schedules, the most efficient treatment was carbogen plus nicotinamide compared to air breathing mice. In a fractionated regime carbogen plus nicotinamide increased also response to radiation.