Outpatient treatment with subcutaneous interleukin-2 and interferon alfa administration in combination with fluorouracil in patients with metastatic renal cell carcinoma: results of a sequential nonrandomized phase II study. Subcutaneous Administration Propeukin Program Cooperative Group.

PURPOSE: We report the results of the Subcutaneous Administration Propeukin Program (SCAPP) II trial of an outpatient treatment in renal cell carcinoma using interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) administered subcutaneously in combination with fluorouracil (5-FU). The objective of this multicenter trial was to confirm that the combination of IL-2, IFN-alpha, and 5-FU leads to a response rate greater than 20%. PATIENTS AND METHODS: Patients with metastatic renal cell carcinoma were included in this study. During the induction phase of the treatment, which lasted 10 weeks, IL-2 and IFN-alpha were administered subcutaneously three times a week for 8 weeks at doses of 18 MIU and 9 MIU, respectively. During these 8 weeks, every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. After evaluation, responding patients or patients with stable disease (SD) were given maintenance treatment, until disease progression (PD) or the appearance of unacceptable toxicity. Each maintenance cycle consisted of a 2-week treatment followed by a three-week rest period. During treatment, IL-2 and IFN-alpha were administered subcutaneously three times a week at doses of 18 MIU and 9 MIU, respectively. Every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. RESULTS: This trial was closed when the sixth sequential analysis showed the lack of benefit from this combination. At the end of the induction period, of 62 patients, 12 (19%; 95% confidence interval [CI], 10% to 31%) reached an objective response, including one complete response (CR), 16 presented with SD, and 27 showed PD. Twenty-seven patients (43%) developed severe toxicity that required reduction of the planned doses (13 patients), delayed treatment (eight patients), or treatment termination (six patients). Seventeen patients were given maintenance treatment. One- and 2-year survival rates were estimated at 55% and 33%, respectively. The 2-year survival rate was 15% in 11 patients who presented with three poor-prognosis factors and 41% in 51 patients who initially presented with no, one, or two poor-prognosis factors (P = .04). CONCLUSION: As in other recently published studies that used 5-FU, IL-2, and IFN-alpha, the multicenter SCAPP II trial in patients with metastatic renal cell carcinoma generated severe toxicity. This sequential trial failed to confirm the favorable results previously obtained by Atzpodien and Sella with this combination of three drugs. Its efficacy, assessed on the response and survival rates, is near to the results observed in programs that used IL-2 alone given subcutaneously.

Radiotherapy in the management of cutaneous epidemic Kaposi's sarcoma.

Between June 1986 and December 1988, we treated 149 patients who had AIDS-related epidemic Kaposi's sarcoma with cutaneous irradiation. According to Mitsayasu's staging, 34 patients (23%) had Stage I disease, 82 (55%) Stage II, 0 Stage III, and 33 (22%) Stage IV. Fifty-eight patients (39%) had previously presented with one or more opportunistic infections. Ninety-four patients (63%) had received previous treatment of their Kaposi's sarcoma: 85 (57%) with interferon and 43 (29%) with vinblastine. Among the 149 patients, we treated 88 (59%) with extended cutaneous irradiation using 4- and/or 8-MeV electron beam energy and 61 patients (41%) with localized irradiation using 45-kVp x-ray energy. The total prescribed dose was 30 Gy: 20 Gy in 2 weeks (2.5 Gy/fraction, 4 times/week), followed by 2 weeks of no irradiation, and then 10 Gy in one week by the same dose schedule. Twenty patients (13%) with edema of the lower limbs were treated using 4-Mv photon therapy with bolus. Of the 131 evaluable patients, 63% achieved a complete remission (CR) and 30% a partial remission (PR) after a mean period of 1.5 months (range: 0.5-3 months). The clinical disease stage, anatomic site, and irradiation technique did not significantly influence the remission rates, although we noticed a higher CR rate when localized irradiation was used (71% vs 55.5% for localized and extended irradiation, respectively; p = 0.08). The overall tolerance was acceptable. Complications were severe epidermitis with skin ulcerations (8% of patients), exudative epidermitis (26%), dry epidermitis (60%), and varying degrees of erythema (6%). Of the 87 patients whose AIDS remained relatively clinically stable during the observation period, recurrences occurred in 56 (64%) after an average of 5.5 months (range: 1.5-12 months). We conclude that radiotherapy is useful and can be recommended as a palliative treatment to relieve pain and physical discomfort or to achieve cosmetic improvements for patients with epidemic Kaposi's sarcoma. We also conclude that radiotherapy is most beneficial in the early stages of disease, when localized treatment is practical.

External irradiation prior to conservative surgery for breast cancer treatment.

From 1981 to 1987, 138 patients with breast cancer unsuitable for primary tumorectomy received initial external radiotherapy (45 Gy/25f/35d) in order to reduce the tumor volume so that secondary limited surgery could be performed. There were 81 T2 and 57 T3. Fifty-seven percent of the patients had a tumor larger than 4.5 cm. After completion of the radiotherapy, 22 patients (16%) showed no more evidence of a tumor either clinically or radiologically and received a boost of 25 Gy. In 52 cases (38%) the tumor regression allowed for secondary tumorectomy followed by a boost of 20 Gy. Sixty-four patients (46%) showed either little or no tumor regression: radical surgery was performed in 14 cases (10%) and high dose boost curietherapy (37 Gy) in the 50 (36%) remaining patients who refused mastectomy. Breast conservation in good condition was thus obtained in 74 patients (54%). Sufficient tumor regression to allow secondary tumorectomy was more often observed in T2 than in T3, in poorly differentiated tumors or mucinous type, and in tumor with well defined mammographic aspects. Actuarial 5-year local control and disease-free survival rates after limited surgery were, respectively, 90% and 73%. No particular complications were observed after secondary tumorectomy. This therapeutic approach is encouraging in patients with large T2 and T3 breast tumors, but a longer follow-up is required to assess definitive conclusions.

Stage I-II squamous cell carcinoma of the oral cavity treated by iridium-192: is elective neck dissection indicated?

This is a retrospective analysis of 233 evaluable patients with stage I-II squamous cell carcinoma of the oral cavity treated by definitive branchytherapy. Minimum follow-up is 3 years. Treatment of neck was chosen by a multidisciplinary team, according to age, medical status and availability for regular follow-up. One hundred and ten patients (47%) underwent elective neck dissection (END); 28 (25%) had positive nodes and received neck irradiation post-operatively. One hundred and twenty three patients (53%) were regularly followed up only, with therapeutic neck dissection (TND) reserved for cases of node relapses. In the END group, there were 19 neck relapses (17%): 12/60 (20%) in patients with mobile tongue carcinoma and 7/50 (14%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 9/19 (47%) cases. In the TND group, there were 21 neck relapses (17%): 16/82 (20%) in patients with mobile tongue carcinoma and 5/41 (10%) in patients with floor of the mouth carcinoma. Salvage treatment was successful in 13/21 (62%) cases. Ten-year survival is 37% for the END group and 31% for the TND group. Tumour stage and infiltration into underlying tissues increased the probability of neck relapse and death. Furthermore, a multivariate analysis showed that patients treated in the TND group had a higher probability of death than patients treated in the END group (p less than 0.04).

Interstitial pneumonitis and venocclusive disease of the liver after bone marrow transplantation.

One hundred and seventy patients were analysed for interstitial pneumonitis and 151 for venocclusive disease of the liver after bone marrow transplantation. We present our results with emphasis on the role of the parameters of single fraction total body irradiation.

Multiple vertebral hemangiomas with neurological signs. Case report.

A case of multiple vertebral hemangiomas with progressive neurological deficit is presented. Successful treatment was accomplished using preoperative embolization, palliative surgical decompression, and postoperative radiation therapy. The patient has remained asymptomatic for 6 years. The authors review the role of current imaging modalities and options for therapeutic intervention. Preoperative embolization, palliative surgical decompression, and postoperative radiotherapy appear to provide a satisfactory outcome in patients with multiple hemangiomas and may represent an effective alternative to more aggressive surgical intervention.

[Network of care for breast cancers: a prospective survey among general practitioners]. / Réseau du soins en cancérologie mammaire: enquête d'opinion prospective auprès des médecins généralistes.

OBJECTIVE: To clarify the general practitioner (GP)'s current perception on a network dedicated to mammary cancers in a rural department. METHODS: A survey by questionnaire was carried out from March to September 1999. This questionnaire made of 3 different sheets and 4 parts entitled "your practice in oncology", the "partnership", "GPs and network", "expectations" respectively, was mailed to 233 GPs board certified by the Conseil Départemental de l'Ordre des Médecins. Questionnaire included space for free comments and a specification sheet. There was no letter of reminder following the first mail. RESULTS: The rate of spontaneous answers was 48% (112/233). Representativeness of the sample was considered coherent with age, sex-ratio, mean duration of setting up, practice modalities in the department of Aube. GPs took care, on annual average, over 6 patients with breast cancer. They generally referred their patients to the oncologist team at the Centre hospitalier général. Such a choice was mainly sustained by the quality of patient reception, the psychological support and the fraternal relationship. GPs were mostly concerned (76%) by the management of both chemotherapy side effects and psychological problems occurring in their patients. By popular request, they wished the setting up of a hot line and a systematic historical reminder of the adverse effects joined to the mail. As far as the network was concerned, 83% of the GPs thought it could be helpful, but only 60% would actively participate. Reasons for such a discrepancy are discussed taking free comments into account. CONCLUSIONS: GPs in the Aube department seem eager to practice in a more collective way, which places the patient in the heart of the medical approach. However they demand to play a key role according both to their knowledge of the whole file and to the trust the patients are putting on them.

[Subcutaneous administration of interleukin-2 in ambulatory treatment of patients with metastatic renal cancer. Three-year results of the SCAPP I program]. / Traitement ambulatoire par interleukine 2 administrée par voie sous-cutanée chez des patients porteurs d'un cancer du rein métastatique. Résultats à 3 ans du programme SCAPP i.

We report a french experience of subcutaneous administration of interleukin-2 in treatment of patients with metastatic renal cell carcinoma. Thirty-nine patients with metastatic renal cell carcinoma were included in the study. During the 10-week induction period, interleukin-2 was administrated subcutaneously 5 days a week for 8 weeks. The weekly dosage were 90 MIU during weeks 1 and 6; 63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, interleukin-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses with 1 complete response. A diminution of dose or interruption of treatment occurred with 7 patients because severe toxicity. Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. The median follow-up of all the patients included was 21 months. The 1, 2 and 3 years survivals were 64%, 33% and 22% respectively. This multicentric trial confirms the efficacity of subcutaneously-administered interleukin-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. Unfortunately, increasing total doses of administrated interleukin-2 does not seem to increase efficacity according to response rate, but is more toxic.

[Total cutaneous electron beam therapy of mycosis fungoides]. / Electronthérapie cutanée totale du mycosis fongoïde.

Electron beam irradiation of the entire skin surface was used to treat 25 patients with mycosis fungoides from 1977 to January 1988. A plexiglas screen was used to reduce the energy of the 8 MeV beam of a Sagittaire linear accelerator to 4 MeV. A total dose of 30 Gy was delivered in 12 fractions over days. This series includes 17 men and 8 women with a mean age of 44 years (range 13-78 years) and a mean follow-up of 34 months (range 6-92 months). The following-up staging system was used: stage A: superficial lesions covering less than 50 p. 100 of the body surface; stage B: superficial lesions covering more than 50 p. 100 of the body surface; stage C: tumors of the skin, lymph nodes and/or visceral organs, Sezary's syndrome. All stage A patients achieved complete remission. One developed recurrent disease in a very limited area 17 months after radiation therapy. No stage A patient died of mycosis fungoides. 6/9 stage B patients achieved complete remission; 4 of these developed recurrent disease localized to the skin 6 to 13 months after electron therapy. These recurrences were controlled by topical nitrogen mustard, puva therapy or localized irradiation. 1 patient showed no response and died of cutaneous mycosis fungoides. 5/10 stage C patients obtained complete remission but all relapsed within a mean period of 7 months. 4/5 of the patients not responding to electron therapy died of their disease and one is alive 16 months after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Vertebral hemangioma with neurologic signs. Therapeutic results. Survey of the French Society of Neurosurgery]. / Hémangiomes vertébraux avec signes neurologiques. Les résultats thérapeutiques. Enquête de la S.N.F.

45 cases of vertebral hemangiomas with neurologic involvement are reported. This series corresponds to the french experience between 1969 to 1988 (series of the "Société Française de Neuro-Chirurgie" (S.F.N.)). In this report, the therapeutic results are detailed. 16 patients were treated by a simple laminectomy, 6 by laminectomy associated with radiotherapy, 4 by radiotherapy alone. In 9 patients, a large removal of the hemangioma was performed by mean of a lamino-arthrectomy (7 cases) or a corporectomy (2 cases). 7 patients were treated by embolization or vertebroplasty. Both techniques were used alone or in association with surgery or radiotherapy. 3 patients had no therapy. Results of the S.F.N. series demonstrated that 75.5% of the patients had a long term favorable clinical course. 13.4% of the patients were not improved. Mortality was of 11.1%. The mean follow up time was of 51.6 months. Recurrence was encountered in 13 cases. It was mainly observed in the first two years. In cases of total involvement of the vertebrae by hemangioma, laminectomy associated with radiotherapy was the best mean of therapy: 93% of recovery without recurrence. Treatment of body localization appeared to be difficult. Corporectomy could be unefficient if a complete removal of the hemangioma could not be performed. In contrast, posterior arch localization was successfully treated by a simple laminectomy without radiotherapy, even in cases of incomplete removal of the hemangioma: all such cases (10 cases) had a complete recovery without recurrence.

[Radiotherapy of vertebral hemangioma with neurologic complications]. / Radiothérapie des hémangiomes vertébraux avec complications neurologiques.

The interest of radiotherapy in the treatment of compressive vertebral hemangiomas (H.V.C.) is discussed from a literature review. Recent advances in imaging permit to precisely define the target-volume. The dose of 35 grays with standard fractioning affords optimal results on H.V.C. with no risk of spinal cord damage.

[Spontaneous rupture of the spleen during the development of chronic pancreatitis. One case]. / Rupture spontanée de rate au cours de l'évolution d'une pancréatite chronique. Un cas.

Spontaneous rupture of the spleen is a relatively rare occurrence during the course of chronic pancreatitis. The physiopathology remains imprecise and mechanical factors are associated with pancreatic enzyme diffusion and vascular changes in explaining its aetiology. The diagnosis is difficult since it often mimics an acute exacerbation of pancreatitis or even actual acute pancreatitis when the existence of the pancreatic condition is not previously known. Abdominal echotomography or peritoneal puncture-lavage and, now, CAT scanning are the key factors in reaching the diagnosis.

[Arterial stenosis after radiotherapy]. / Les sténoses artérielles après radiothérapie.

Published reports of arterial stenosis following radiotherapy are reviewed. In oncological practice, this complication is rare but experimental studies have demonstrated the role of irradiation in producing arterial lesions. The histological specificity and the mechanisms of radiation and related arterial lesions are discussed. Atherosclerosis risk factors and chemotherapy could have a synergic role on artery stenosis. Cases reported of arterial stenosis after radiotherapy include subclavicular artery after breast cancer, carotid artery after head and neck cancer, coronary artery and abdominal aorta or its trunks after pelvic and abdominal irradiation. The radiotherapy parameters described are not unusual. Therapeutical modalities and their indications are presented.

Subcutaneous recombinant interleukin-2 (rIL-2) in out-patients with metastatic renal cell carcinoma. Results of a multicenter SCAPP1 trial.

BACKGROUND: This multicenter phase II trial was conducted in order to evaluate the efficacy and toxicity of the subcutaneous route of administration of rIL-2 in the treatment of patients with metastatic renal cell carcinoma and to check whether an increased cumulative dose of rIL-2 increases efficacy. PATIENTS AND METHODS: Thirty-nine patients with metastatic renal cell carcinoma were included in this study. During the induction period, rIL-2 was administered subcutaneously 5 days a week for 8 weeks. The weekly dosages were 90 MIU during weeks 1 and 6;63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, rIL-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. RESULTS: After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses (95% CI: 9% to 37%) with one complete response. Treatment was interrupted or reduced due to toxicity for seven patients: Neuropsychiatric symptoms (3 patients), joint pain (1 patient), major asthenia and anorexia (1 patient), stroke (1 patient), and septicemia (1 patient). Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. In none of the patients did the response status improve during this maintenance period. The median follow-up of all of the patients included was 19 months. The one- and two-year survivals were 65% and 33%, respectively, ad the median duration of response was 11 months (5 to 16+). CONCLUSIONS: This multicentric study confirms the efficacy of subcutaneously-administered rIL-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. The role of a maintenance therapy needs further evaluation.