Phase II study of cytarabine and etoposide in children with refractory or relapsed non-Hodgkin's lymphoma: a study of the French Society of Pediatric Oncology.

Twenty-five children or adolescents with relapsed or refractory non-Hodgkin's lymphoma (NHL) were included in this phase II study of the combination of cytarabine (ARA-C) 50 mg/m2/d by 12 hours continuous infusion day 1 to day 5, ARA-C 3 g/m2/d in 3 hours day 1 to day 4, and etoposide (VP 16) 200 mg/m2 daily from day 1 to day 4. Twelve patients had B-cell, 12 T-cell, and one non-T, non-B-cell lymphoma; according to Murphy's staging system, 15 had stage III and nine stage IV disease with bone marrow involvement at diagnosis. All had previously received ARA-C by push or continuous infusion. Two patients had received epipodophyllotoxins. At the time of the study, three children had initial refractory disease, 18 were in first relapse (14 on therapy), two in first refractory relapse, and two in second relapse (on therapy). The overall response rate (RR) was 60%: eight complete responses (CRs), seven partial responses (PRs) (two became CRs after a second course). The RR was 66% (four CRs plus four PRs) in B-cell and 54% (four CRs, three PRs) in non-B-cell NHL. It was 20% (one PR per five patients) in initial or relapsed refractory disease. In four patients with measurable CNS disease, there were three CRs. Duration of response was nonassessable since all the responding patients received high-dose polychemotherapy followed by autologous bone marrow transplantation (ABMT) (five are alive with long follow-up [FU]). Toxicity was marked mostly by pancytopenia for 2 weeks, and half the patients encountered a grade-3 infection. One severe diarrhea was observed. In conclusion, high-dose ARA-C (HD-ARA-C) and VP 16 are an effective regimen in relapsed NHL, especially with CNS disease, and its toxicity is acceptable with regards to the prognosis of the disease.

Treatment of poor prognosis Burkitt's lymphoma in adults with the Société Française d'Oncologie Pédiatrique LMB Protocol--a study of the Federation Nationale des Centres de Lutte Contre le Cancer (FNLCC).

14 adult patients between 16 and 50 years old with small non-cleaved cell lymphoma (Burkitt's lymphoma) were prospectively treated from 1982 to 1990 with the LMB protocols of the Société Française d'Oncologie Pédiatrique (SFOP). No HIV-positive patients were included. All patients had extensive disease with bad prognosis factors, i.e. 10 patients had Murphy stage III and 4 had stage IV with bone marrow involvement. The LMB protocols were characterised by high-dose fractionated cyclophosphamide, high-dose methotrexate (HD-MTX), and cytosine arabinoside. No local or central nervous system irradiation was used. Treatment duration ranged from 5 (LMB 84) to 12 (LMB 81) months. There were no therapy-related deaths. All patients achieved complete remission (CR). 6 patients relapsed between 2 and 30 months following CR. 8 of the 14 patients (57%) are still alive and disease-free after treatment by LMB protocol alone. 2 patients were salvaged with bone marrow transplantation after relapse and a total of 10 out of 14 patients (71%) are disease-free at the time of this report. Our results showed the high curability of advanced Burkitt's lymphoma using a paediatric protocol, even in adult patients. The LMB protocol may be applied to adult patients but requires intensive care during the induction period.

Non-metastatic Ewing's sarcoma of the ribs: the French Society of Pediatric Oncology Experience.

From 1984 to 1997, 57 consecutive patients with non-metastatic Ewing's sarcoma of the ribs were treated according to multimodal French Society of Pediatric Oncology (SFOP) protocols EW 84, EW 88 and EW 93. The results of treatment were reviewed and analysed. Median age was 12 years. 34 patients had large tumours (greatest tumour dimension > or = 8 cm); pleural effusion was noted in 26. A tumour-positive margin after surgery was noted in 15 patients. Histological response after chemotherapy was assessed in 34 patients. 34 patients received radiation therapy. With a median follow-up of 5 years, the projected overall and relapse-free survival rates were 69 and 62%, respectively. The major site of relapse was local. None of the following was significant in predicting relapse: tumour size, gender, age at diagnosis, existence of pleural effusion, level of rib tumour, rib component, type of local control, surgical margin (positive or negative). Response to chemotherapy was the sole significant prognostic factor (P=0.004). Patients with pleural effusion had a higher percentage of relapse if they were treated without local radiation therapy. Our study confirms the prognostic significance of response to initial chemotherapy. Radiation therapy may be withheld in selected cases, but seems necessary in patients with pleural effusion.

Ifosfamide and etoposide in childhood osteosarcoma. A phase II study of the French Society of Paediatric Oncology.

The aim of this phase II study was to determine the efficacy of high-dose ifosfamide with moderate dose etoposide in childhood osteosarcoma. From January 1992 to January 1995, 27 children (15 male, 12 female) with relapsed or refractory evaluable osteosarcoma were included in a phase II study of two courses of ifosfamide 3g/m2/day and etoposide 75 mg/m2/day for 4 days. Median age was 14 years (7-19 years). All but one had received high-dose methotrexate and doxorubicin as first-line treatment. 22 patients had previously received ifosfamide. This regimen was given as first-line in 1 patient, second-line in 23 and third-line in 3. Evaluable disease was lung metastases in 21 patients, local relapse in 5 and adenopathy in 1. There were six complete responses, seven partial responses, three minor responses, six stable disease and five progressive disease (including one mixed response). Response rate was 48% (95% confidence interval, 29-67%). Duration of response was not available (10 responding patients had other treatments). Response rate was equivalent in the subgroup of 22 patients who had previously received ifosfamide (4 CR, 6 PR). Among 3 patients who received the phase II regimen as third-line chemotherapy, there was 1 PR. All but 4 patients had a well tolerated grade 4 neutropenia. Transient mild confusion or seizures were each observed once. 5 patients are alive 15-31 months after the beginning of chemotherapy. This combination of drugs at this dosage has tolerable toxicity, is efficient and deserves evaluation in phase III studies.

Sequential measurement of intratumoral platinum concentration in cervix uterine tumors after cis-dichlorodiammineplatinum (CDDP) administration.

Intratumoral (cervix uterine tumors) distribution of platinum was studied in ten patients after IV administration of CDDP. Sequential tumoral measurement of platinum was carried out 4, 24, and 48 h after the IV infusion. Platinum concentration in the tumor samples ranged from 0 to 29,5 ng/mg tissue. For all patients, there was no definite evolution of the tumoral concentration with time and there was no good relation for the same patient between the platinum concentration in three successive biopsies. These results involve uncertainty in studies attempting to relate CDDP tumor levels (measured in one biopsy) and tumor response to chemotherapy.

An evaluation of CA 549, a circulating marker of breast cancer using a procedure for comparison with CA 15.3.

A serum assay of CA 549 (Hybri-BREScan CA 549 degrees, Hybritech), a new tumor marker, was performed in 129 patients with breast cancer and 35 healthy women, in parallel with CA 15.3 (ELSA-CA 15.3 degrees, CIS Biointernational). Comparing 95 women with primary breast carcinoma and 35 controls, Relative (or Receiver) Operating Characteristic (ROC) analysis revealed that the Area Under ROC Curve (AUC) of CA 15.3 was significantly higher than that of CA 549, indicating that, for our population, the first marker was more effective. Parallel and series analyses were also performed using ROC AUC and revealed that the combination of these two tests did not give more information than the CA 15.3 test alone; however, they did not in any way constitute diagnostic tools. In our experience, the best field of application for CA 549 seems to be the therapeutic monitoring and early detection of breast cancer recurrences. However, further investigations on a larger scale are necessary to assess more precisely the place of CA 549 in following the clinical course of breast cancer patients.

The informative content of radiography and scintigraphy in the diagnosis of bone metastases after breast cancer.

In this paper we apply decision theory to evaluate the efficiency of diagnostic procedures. In the case we discuss, we compute the value of scintigraphy and radiography used separately or in combination in the diagnosis and treatment of bony metastases after breast cancer.

Cerebellar medulloblastoma: results of multidisciplinary treatment. Report of 120 cases.

The authors report a series of 120 cerebellar medulloblastomas. All patients were operated on between 1953 and 1982. Among them, 88 completed the treatment with radiotherapy, and 32 had additional chemotherapy. The operative mortality was 22.5%. The 5-year survival rate was 30% in the whole series. Recurrences occurred in 35 patients, associated with supratentorial or spinal metastasis in 60% of cases.

[Breast neoplasms: information in question(s). A survey of patients and physicians at a cancer treatment center]. / Cancer du sein: l'information en question(s). Enquête auprès des patientes et des médecins d'un Centre de lutte contre le cancer.

OBJECTIVE: The aim of this study was to know the wishes of our patients for information and to compare them with the point of view of our colleagues in a cancer center. METHODS: We gave 100 consecutive new patients with breast cancer a questionnaire about their needs. The same questionnaire was given in duplicate to all our colleagues in the cancer center (n = 53) asking: 1) their own needs of information if they had breast cancer 2) how they thought the patients would answer. RESULTS: Seventy-five percent of the patients and 81% of the doctors returned the questionnaire (28 were men and 15 women; 81% were involved in the management of breast cancer). On one hand, concerning information about the disease and about the treatment, there was no difference between the needs expressed by patients of doctors (as patients). As expected, the two groups wanted to be well informed. On the other hand, there was always a statistically significant difference between the needs expressed by patients and the opinion of doctors who systematically underestimated them. Concerning information to the family, 21% of doctors and only 4% of patients didn't want any information to be given to their family. Interestingly, 67% of the patients thought the decision had to be taken together with the doctor and 56% of the doctors (as patients) wished the decision to be taken by the doctor. CONCLUSION: Patients and physicians if they were patients, expressed the same high level need of information, but the patients needs seemed underestimated by the majority of doctors.

[Carcinoma in situ of the uterine cervix. Experience of the Centre Oscar Labret of Lille (author's transl)]. / L'épithélioma intra-épithélial du col utérin. Expérience du Centre Oscar Lambret de Lille.

Forty cases of carcinoma in situ of the cervix were seen in the "Center Oscar Labret" of Lille between 1953 and 1978. The best treatment appears to be only simple total hysterectomy. Twenty patients underwent such an operation. seven In the course attended of follow-up, among 36 patients who regularly the out-patient clinic, there was one case of persistent progression and one early vaginal recurrence of the carcinoma in situ.

[High dose ifosfamide at 15 g/m2/cycle: a feasibility study in 10 patients]. / L'ifosfamide à hautes doses 15 g/m2/cure. Etude de faisabilité chez 10 patients.

Ifosfamide is one of the most efficient antimitotic in soft tissue sarcoma. To try to find a possible dose-effect, 10 patients with advanced pretraited relapsed soft tissue sarcoma received 15 g/m2/cycle ifosfamide in continuous infusion during 5 days. A pharmacokinetic study was done for 2 patients. All patients received growth factors, ondansetron and 8 clonazepam. Renal toxicity was evaluated after the first and the second cycle. Twenty two cycles were delivered to patients who have been already treated with ifosfamid (10 patients with 15 g/m2 to 54 g/m2, median 27 g/m2) or cis platinum (2 patients). No major renal or neurologic toxicity was observed; only subclinical modifications of urinary enzymes excretion were found. Two patients had visual hallucinations at the end of a cycle and just in the 2 following days; another presented a neuropathy of inferior limbs. Hematological toxicity was very limited. Pharmacokinetic study did not show induction mechanism at this dosage and with this type of administration. So ifosfamide 3 g/m2 during 5 days is feasible. The few level of complications observed is perhaps linked to the daily dose of 3 g/m2 instead of 4 g/m2 or more used in the other studies.

[Chemotherapy and dental growth]. / Chimiothérapie et croissance dentaire.

A prospective study about the development of the mandibular second right molar, has been performed with 17 chemotherapy treated children in the Paediatric Oncology department of the Centre Oscar-Lambret (Lille). Our method is based upon the measure of the crown or root length for different periods: periods with or without chemotherapy. These measurements have been performed every 6 months for 18 months with orthopantomograms. We notice for both the crown and the root: a significant difference in growing speed between periods with an without chemotherapy; a speeding up of the mineralization at the end of the treatment rejoining the average figures of a healthy test population.

[Karyotype of peripheral blood lymphocytes in patients treated for Hodgkin disease]. / Le caryotype des lymphocytes sanguins périphériques des hodgkiniens traités.

Peripheral lymphocyte chromosomes were analyzed in 55 consecutive patients with complete remission after treatment for Hodgkin's disease. In 8 patients, observed metaphases were too few in number. The other 47 patients, 29 men and 18 women, had been off all therapy for 53 months (median 41, ext. 1 to 250 months). The mean interval since the diagnosis was 78 months (median: 73 months) and the mean age at the time of chromosome analysis was 38 years (median: 34, ext. 10-78 years). No patient had either a preleukemic syndrome or leukemia. In contrast to karyotypes in normal controls and previously untreated patients, abnormal cells, hypodiploid, hyperdiploid and tetradiploid cells were more frequent. But neither monosomy 5 or 7 nor trisomy 8 were observed. Intrachromosomal rearrangements (gaps, breaks...) were significantly more frequent (12% vs 5% in untreated patients) particularly on chromosomes 1 and 2. Interchromosomal rearrangements were also numerous (1,25%) but no cells showed any specific translocation for malignant hemopathy. Chromosomal aberrations do not seem closely associated with treatments but influenced by the post-diagnosis interval and the factors present at the time of primary treatment.

[Nasopharyngeal epitheliomas: experience of the Regional Cancer Control Center in Lille (79 cases 1970-1982)]. / Les épitheliomas nasopharyngés: expérience du Centre Régional de Lutte contre le Cancer de Lille (79 cas de 1970 à 1982).

From 1970 to 1982, 79 cases of nasopharyngeal carcinomas were treated at the Regional Cancer Center of Lille (France). At the term of the study, it appears that patients of Central Europe origin have a rather high risk of NPC (17% of cases, that ethnic population representing about 8% of all superior aerodigestive tract carcinomas). The classical differences between well and undifferentiated tumors are founded, the first presenting local spread the other general involvement.

[Atypical decubitus fibroplasia: a recent entity. Apropos of a case of an adolescent girl]. / La fibroplasie atypique de décubitus: une entité récente. A propos d'un cas chez une adolescente.

Atypical decubital fibroplasia (FAD) occurs especially in elderly and physically debilited or immobilized patients. We report one observation which is peculiar due to the patient's young age and its circumstances. The painless mass is situated in hyperpressure areas (shoulder, posterior or lateral chest wall, sacrum). The lesion is situated in the deep subcutis and has ill defined limits; it is characterized by zones of fibrinoid necrosis and fibrosis and a prominent myxoid stroma. The differential diagnoses includes mesenchymatous malignant tumors and non neoplastic fibroblastic proliferations such as proliferative fasciitis and decubitus ulcer. The prominent underlying factor and the initial event contributing to its pathogenesis seems to be ischemia. Although some recurrent cases have been reported, FAD is a benign lesion whose treatment is surgical removal.

[The reproduction in France of Rosen's protocol for osteosarcomas]. / La reproduction en France du protocole de Rosen pour les ostéosarcomes.

The authors treated 188 patients with osteosarcoma by chemotherapy followed by surgery and additional chemotherapy (Rosen's T regimen). In 14% of cases, infectious, neurologic or cardiac complications were observed, which resulted in death in 2% of the patients. Forty-six per cent responded well to the primary chemotherapy, 76% of which are alive and disease-free, as opposed to merely 42% of the bad responders.

[Malignant germinal tumors of the thyroid. 2 cases]. / Tumeurs germinales malignes de la thyroïde 2 observations.

Malignant germinal tumours of the thyroid gland are exceptional. Two cases are reported here. The first case concerned an 8-year old girl who had a teratoma; she was treated by surgery and adjuvant chemotherapy; 4 years after the diagnosis she is still alive and in complete remission. The second case is that of a 21-year old woman with a vitelline sac tumour treated by surgery and radiotherapy; she soon had lung metastases and died. The diagnostic, prognostic and therapeutic aspects of malignant germinal tumours of the thyroid gland are presented, together with data from a review of the literature. The authors insist on the importance of marker assays for all thyroid tumours with suspicious cytology. These tumours should be treated by surgery and initial chemotherapy combined, just as malignant germinal tumours located in other organs.

[Malignant melanoma in children and adolescents. 8 cases]. / Les mélanomes malins de l'enfant et de l'adolescent. Huit observations.

Eight cases of malignant melanoma developed during childhood have been recorded over a 35-year period. Treatment and course of the disease were extremely variable. Melanomas developed on giant pigmented naevi had a particularly somber prognosis: death occurred within 6, 7 and 3 months respectively in the 3 cases observed. In the 5 remaining cases, the course of the melanoma seemed to be about the same as in adults. The main difficulty resides in the clinical and histopathological diagnosis at that age: although most lesions are benign, uncertainty is not permissible, and in doubtful cases the tumour must be rapidly removed and examined.

[Value of the assay of squamous cell carcinoma in cancer of the uterine cervix]. / Intérêt du dosage de l'antigène "squamous cell carcinoma" dans le cancer du col utérin.

The squamous cell carcinoma (SCC) antigen was assayed by radioimmunoassay in patients with squamous cell carcinoma of the uterine cervix at different stages before any treatment and in patients under treatment. Low levels of SCC antigen were detected in the early stages of the disease, showing that this antigen cannot be considered an aid to diagnosis. In the more advanced cancers, an increase of SCC antigen levels proportional to the stage of the disease was observed. However, SCC antigen assays are mainly useful in the follow-up of patients to evaluate therapeutic effectiveness.

[Mirror-image osteosarcoma of the radius. A case]. / Ostéosarcome en miroir du radius. Une observation.

Multiple osteosarcoma is a rare tumour which usually has a poor prognosis. We report the case of a 14-year old girl who developed successively, at 2 1/2 years' interval, one osteosarcoma of the right radius bone, then one of the left radius bone. The tumours were strictly symmetrical. Each time, the patient was treated with chemotherapy of the Rosen type and underwent conservative surgery. At present, 5 years after the first treatment, she is in good health. This case is remarkable on several scores: chemotherapy was feasible and well tolerated, the multiple osteosarcoma had a favourable outcome, and conservative surgery of both radius bones gave satisfactory functional results.