[Resection of iliac vessels and adnexial cancer: report of 2 cases]. / Résection vasculaire et cancers annexiels : à propos de 2 cas.

Aim of no residual macroscopic disease has to be the objective of the gynecologist oncologist surgeon. It can require extensive surgical procedures in all the abdomen area. We report 2 rare cases of cytoreductive surgery with iliac vessels resection and use of vascular prosthesis. We discuss the opportunity of this surgery with high morbidity.

Contralateral axillary involvement in breast cancer recurrence: locoregional disease or metastasis?

We describe a case of right mammary homolateral recurrence with controlateral axillary invasion. The absence of occult involvement of the left breast was confirmed by MRI. A subsequent thoraco-abdomino-pelvic scan and bone scintigraphy did not reveal any metastases. Lymphoscintigraphy of the right breast, after periareolar injection, revealed lymphatic drainage from the right breast into the left contralateral axillary lymph node. Because of the changes in axillary drainage after mammary and axillary surgery observed by lymphoscintigraphy, contralateral axillary involvement could be considered as locoregional disease in the same way as homolateral lymph node involvement.

Oral vinorelbine/paclitaxel combination treatment of metastatic breast cancer: a phase I study.

PURPOSE: Intravenous (i.v.) vinorelbine (VRL) generally given on days 1 and 8 of an every three-week cycle in combination with paclitaxel (PTX) is an effective option for the treatment of metastatic breast cancer (MBC). In an effort to improve both patient and chemotherapy unit convenience, oral VRL was used at equivalent doses of i.v. VRL. PATIENTS AND METHODS: The maximal tolerated dose (MTD) was determined during the first cycle of oral VRL given on days 1 and 8 or 15 and PTX infused over 3 h on day 1 every 3 weeks, maximum of 6 cycles. The dose of oral VRL was escalated from 60 to 80 mg/m2 in 10 mg/m2 increments. Paclitaxel was administered at 110 and then 135 mg/m2. The combination regimen was given as first-line chemotherapy of MBC. Three to six patients per cohort were treated. RESULTS: Twenty-two patients were treated in the first four cohorts (oral VRL/PTX): 60/110, 70/110, 80/110 and 80/135. In cohort 4, seven patients were treated, one patient being non-evaluable for MTD, three of them presented a dose-limiting toxicity (DLT) consisting of febrile neutropenia and neutropenic infection. Therefore 80/135 was the MTD. Because 36% of oral VRL administrations on day 8 were delayed to day 15 at 80/110, two additional cohorts were tested: in cohort 5, oral VRL 60 mg/m2 on days 1 and 15 and PTX 135 mg/m2 on day 1 and in cohort 6, oral VRL 80 mg/m2 on days 1 and 15 and PTX 110 mg/m2 on day 1, every 3 weeks. In cohort 5, six out of eight patients had DLTs: omission of oral VRL on day 15 for five patients, grade 4 neutropenia>7 days for another one. Therefore the recommended dose (RD) for further clinical testing was oral VRL 80 mg/m2 on days 1 and 15 and PTX 110 mg/m2 on day 1 of an every 3-week cycle. Two of the three evaluable patients treated at the RD had a partial response. The pharmacokinetics of VRL and PTX is being analysed and will be further presented in a separate publication. CONCLUSIONS: This phase I study has determined the doses of oral VRL and PTX to be used in combination for the benefit of the patient and of the chemotherapy unit in term of nurse's workload. The recommended regimen of oral VRL 80 mg/m2 on days 1 and 15 and PTX 110 mg/m2 on day 1 given every 3 weeks will be further tested in phase II.

Pre-operative systemic (neo-adjuvant) therapy with trastuzumab and docetaxel for HER2-overexpressing stage II or III breast cancer: results of a multicenter phase II trial.

BACKGROUND: Trastuzumab plus chemotherapy has become the standard of care for women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Trastuzumab-based pre-operative systemic (neo-adjuvant) therapy (PST) also appears promising, warranting further investigation. PATIENTS AND METHODS: Patients with HER2-positive, stage II/III non-inflammatory, operable breast cancer requiring a mastectomy (but who wished to conserve the breast) received weekly trastuzumab and 3-weekly docetaxel for six cycles before surgery. The primary end point was pathological complete response (pCR) rate, determined from surgical specimens. RESULTS: Thirty-three patients were enrolled. The majority (79%) had T2 tumors, with 42% being N1/2. Twenty-nine patients completed six cycles of therapy and one patient withdrew prematurely due to progressive disease. A complete or partial objective clinical response was seen in 96% (73% and 23%, respectively) of patients. Surgery was performed in 30 patients, breast conserving in 23 (77%). In an intention-to-treat analysis, tumor and nodal pCR was seen in 14 (47%) patients. Treatment was generally well tolerated. Grade 3/4 neutropenia occurred in 85% of patients while febrile neutropenia was encountered in 18%. Only three patients withdrew prematurely due to toxicity. No symptomatic cardiac dysfunction was reported. CONCLUSIONS: PST with trastuzumab plus docetaxel achieved promising efficacy, with a high pCR rate and good tolerability, in women with stage II or III HER2-positive breast cancer.

Emergence of type 2 diabetes in an hospital based cohort of children with diabetes mellitus.

OBJECTIVES: Increasing awareness of the heterogeneity of diabetes mellitus (DM) at presentation is changing our approach to this disease. We used the 1999 American Diabetes Association (ADA) criteria to determine the distribution of DM patterns in a large pediatric cohort with the aim of documenting the emergence of type 2 diabetes mellitus. MATERIAL AND METHODS: Charts of diabetic children aged 1 to 16 years and admitted to our center between 1993 and 1998 were reviewed for data needed to achieve classification of the type of diabetes mellitus. RESULTS: Of the 382 study patients, 327 (85.6%) had autoimmune type 1 DM (clinical insulin-treated type 1 DM with immunologic and/or genetic evidence of autoimmunity) and 6 (1.6%) had idiopathic type 1 DM (clinical insulin-treated type 1 DM without evidence of autoimmunity). Four (1.0%) patients met all the criteria for type 2 DM; all were obese and three had acanthosis nigricans; in one the diagnosis was changed from type 1 to type 2 DM during follow-up. Four patients could be classified as lean patients with type 2 DM. In keeping with recent reports of a rise in the incidence of type 2 DM, 6 of these type 2 cases were diagnosed in the last year of the study. CONCLUSION: The ADA classification helps to understand the pathophysiology of pediatric DM, thus providing useful therapeutic guidance. At presentation, most cases of pediatric DM are type 1, but we show here that type 2 DM becomes now a diagnosis to consider although in children. Our study, from a one large study center is not an epidemiological one but is consistent with population studies. Systematic or targeted screening for type 2 in children should be discussed.

Results of a phase II trial with second-line cystemustine at 60 mg/m2 in advanced soft tissue sarcoma: a trial of the EORTC Early Clinical Studies Group.

The aim of this phase II trial was to examine the efficacy of a new nitrosourea, cystemustine, in soft tissue sarcoma. Between January 1990 and March 1991, 32 pretreated patients with advanced soft tissue sarcoma were enrolled. Cystemustine was given every 2 weeks at 60 mg/m2 via a 15-min i.v. infusion. All eligible patients were considered evaluable for response and toxicity (WHO criteria). Of the 32 enrolled patients, 4 were ineligible, leaving 28 evaluable patients. All but 1 had been pretreated: 6 with adjuvant chemotherapy, 18 patients with first-line palliative chemotherapy without nitrosourea, 3 with both treatments, and 18 had received radiotherapy. Median age was 54 years (range 20-73) and median performance status was 1 (0-2). One partial response (PR, duration 12 weeks), 2 stable disease and 25 progressions were observed, giving an overall response rate of 3.57% (confidence interval: 0.1-18.4%). Toxicity was mild, and was mainly neutropenia (no grade 3 or 4), thrombocytopenia (3.57% grade 3 and grade 4) and nausea-vomiting (no grade 3 or 4). It should be noted that the treatment for the patient who obtained a PR was third line with no previous response. Cystemustine with this schedule appears to have a low clinical activity and toxicity in advanced soft tissue sarcoma.

AcSDKP plasma concentrations in patients with solid tumours: comparison of two chemotherapeutic regimens.

The tetrapeptide AcSer-Asp-Lys-Pro (AcSDKP) is a physiological inhibitor of the proliferation of haematopoietic stem cells and progenitors. In Ara-C-treated mice, its plasmatic concentrations decrease while the CFU-S start cycling. Infusion of synthetic AcSDKP (Goralatide) at this time protects them from haematoxicity by blocking early cycling of CFU-S. Both in vitro and in vivo, this effect seems to be optimal in a narrow range of concentrations. Thus, a better knowledge of the kinetics of endogenous AcSDKP during cancer treatment could help to optimize the treatments with Goralatide. AcSDKP plasma levels have been measured by a specific EIA in 14 cancer patients during the two initial monthly 5 day courses of chemotherapy with 5-FU alone administered either by continuous infusions (six patients) or by 1 h daily infusions (eight patients). AcSDKP concentrations did not vary significantly during the first and the second course. Together with our previous results in AML patients treated with high doses chemotherapy (Ara-C and Anthracyclin), our present data suggest that the variations of endogenous AcSDKP in patients are dependent of the type, doses and schedule of chemotherapy.

Inflammatory carcinomas of the breast: a clinical, pathological, or a clinical and pathological definition?

Some controversy remains about the clinical or pathological definition of the different types of inflammatory breast cancer (IBC) and especially the diagnostic and prognostic value of dermal lymphatic involvement. Our purpose was to classify the different types of IBC for which diagnosis was confirmed intraoperatively and ascertain features allowing reliable diagnosis. We studied clinical findings, biological data, and treatment outcome in a series of 144 successive patients. Our results suggest that there are 2 biologically different entities i.e., true IBC and pseudo-IBC. True IBC, whose course is currently fatal in all cases, can be divided into 2 sub-categories i.e., common true IBC (75.7% of cases), in which inflammatory signs occur primarily or secondarily, and occult true IBC (13.2% of cases). Dermal emboli have been observed in 61% of common true IBC, but their absence did not alter the rapidly unfavourable outcome. Extensive lymph-node involvement, other biological features and survival were the same in the 2 sub-categories. Pseudo-IBC (11.1% of cases) can easily be confused with common true IBC. The biological characteristics of pseudo-IBC differ from those of true IBC: no dermal lymphatic involvement and little or no lymph-node involvement. Despite large tumour size, outcome was particularly favourable. It is of great importance to differentiate true and pseudo-IBC, for which the treatments are different. Confirmation of true IBC requires pathological demonstration of dermal lymphatic emboli or extensive lymph-node involvement. Occult IBC must be identified for patients presenting rapidly growing tumours.

Phase II randomized study of paclitaxel versus mitomycin in advanced breast cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been shown to be an effective agent in the treatment of metastatic breast carcinoma. This multicenter randomized study compared paclitaxel 175 mg/m2 given as a 3-hour infusion every 3 weeks with mitomycin 12 mg/m2 given as an intravenous infusion every 6 weeks. Eighty-one patients have been randomized, and preliminary results of a planned analysis of the first 36 evaluable patients per arm are reported. Pretreatment characteristics were well balanced between the two groups. All patients previously have received chemotherapy for metastatic disease, and half had both adjuvant therapy and chemotherapy for metastatic disease. All but one patient previously had received anthracyclines. Of the first 81 randomized patients, 72 were evaluable for response and toxicity (four never treated, five concomitant hormonotherapy). Partial responses were seen in 17% of patients in the paclitaxel arm and 6% in the mitomycin arm (P = .14). Crossover to paclitaxel therapy following progression on mitomycin achieved an objective response rate of 24% (five of 21 patients). Responses to paclitaxel therapy lasted for a median duration of 9.1 months (range, 6.2 to 12+ months). Median time to progression was significantly longer in the paclitaxel arm (3.5 months v 1.6 months; P = .026). The quality-of-life-adjusted analysis confirmed the advantage of paclitaxel therapy, even when the delay of disease progression was adjusted for important adverse events. Adverse events, most importantly neutropenia and neuropathy, were more frequently observed in the paclitaxel arm. However, patients remained on paclitaxel therapy for many more courses than did those treated in the mitomycin arm. In conclusion, paclitaxel 175 mg/m2 given as a 3-hour intravenous infusion has been demonstrated to be an active agent in the treatment of chemotherapy-refractory advanced breast cancer, even after therapy with mitomycin has failed.

Age as a prognostic factor in breast cancer: relationship to pathologic and biologic features.

The relationship of age with prognostic factors and outcome of breast cancer has long been controversial due to numerous confounding factors. In order to clarify the prognostic value of age, we analyzed a homogeneous population of 1,266 patients treated for breast cancer at the same institution (mean follow-up: 62 months). Three groups were compared: patients under 35 years of age, non-menopausal patients over 35 years of age, and post-menopausal patients under the age of 70 years. A higher frequency of undifferentiated tumors, histoprognostic grade-3 cancer, microscopic lymph-node involvement and negative hormonal receptor status was observed in patients under 35 years. In addition, clinical but not anatomical tumor size was greater in young patients, suggesting higher stromal activity. Metastasis-free survival and overall survival were significantly poorer before 35 years. Differences were observed when patients were matched with regard to stage, anatomic size, histoprognostic grade, microscopic lymph-node involvement and receptor status. Multivariate analysis of both overall and metastasis-free survival demonstrated that age younger than 35 years was an independent risk factor. Younger women had a higher risk of local recurrence but, unlike older women, they did not experience any worsening of the already unfavorable outcome due to recurrence.

Taxol (paclitaxel) safety in patients with platinum pretreated ovarian carcinoma: an interim analysis of a phase II multicenter study.

The objective of this phase II, multicenter, prospective study was to evaluate the safety and the response rate of paclitaxel administered to patients with ovarian cancer. Eligible patients had histologically proven ovarian carcinoma and measurable or evaluable disease and had received at least one platinum-containing regimen and no more than three prior chemotherapy regimens. Paclitaxel was given as a continuous intravenous (i.v.) infusion over 3 hours every 3 weeks. Dose was determined by the number of prior chemotherapy regimens. Patients with one or two prior chemotherapy regimens received 175 mg/m2 (group A) and patients with three prior chemotherapy regimens 135 mg/m2 paclitaxel (group B) after premedication. Treatment was repeated every 3 weeks. An interim safety analysis for the first 99 evaluable patients, 72 treated with 175 mg/m2 and 27 treated with 135 mg/m2 paclitaxel, is reported here. Median number of courses analyzed per patient was four (range, 1 to 6) in the two groups, for a total of 393 courses evaluable for toxicity (286 in group A, 107 in group B). World Health Organization (WHO) grade 3-4 neutropenia was observed in 29.6% of courses in group A and in 23.3% in group B. Two group A patients, 1 at courses 3 and 4 and 1 at course 6, experienced WHO grade 2 fever or infection associated with a WHO grade 4 neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Seraspenide (acetylSDKP): phase I-II trial study of inhibitor of hematopoiesis protects against toxicity of aracytine and ifosfamide monochemotherapies]. / Séraspénide (acétylSDKP): étude en phase I-II d'un inhibiteur de l'hématopoïèse la protégeant de la toxicité de monochimiothérapies aracytine et ifosfamide.

Seraspenide, a synthetic tetrapeptide, inhibits cell cycle entry of normal hematopoietic stem cells. In mice it protects hemopoiesis against the damage caused by cytarabine, cyclophosphamide and carboplatin. Seraspenide has been given to 53 cancer patients undergoing monochemotherapy with cytarabine and ifosfamide in a double-blind cross-over randomized study. A significant protection of peripheral blood cells has been observed. Seraspenide has been devoided of toxicity.

Inflammatory carcinoma of the breast.

Inflammatory breast carcinoma has to be defined by accurate clinical and pathological criteria. The prognosis is very poor and improvements made by chemotherapy are limited to the increase in the disease-free period and overall survival for a few months.

c-myc gene amplification in selected node-negative breast cancer patients correlates with high rate of early relapse.

In breast cancers with histologically negative axillary nodes selected for high frequency of recurrence, the amplification of c-myc, erbB-2 and int-2 genes was found to concern, respectively 25% (16/65), 31% (25/81) and 14% (10/70) of tumours. Their relation with tumour progression expressed by relapse-free survival is reported. Using univariate analyses, c-myc amplified tumours showed significant association with early (30-month period after diagnosis) (P = 0.0013) and intermediate (50-month period after diagnosis) (P = 0.0398) risks of recurrence. In contrast, only a trend towards higher relapse was observed in erbB-2 amplified breast cancers with respect to later events (occurring over the first 30-month period). Multivariate analyses indicated that c-myc amplification is an independent prognostic factor stronger than oestrogen receptor status and tumour size to define a high risk subset in node-negative patients selected for high frequency of recurrence.

Surface CD4 density remains constant on lymphocytes of HIV-infected patients in the progression of disease.

In an attempt to question the influence of circulating virus, soluble gp120 or CD4 self-reacting antibodies upon results of CD4+ T-cell immunophenotyping in AIDS patients, five anti-CD4 mAb defining several epitopes of the V1 and V2 domains of the CD4 molecule were used to analyse the epitopic density of CD4 on lymphocytes of seropositive patients taken at stages II, III and IV of HIV infection, according to the Centers for Disease Control (CDC, Atlanta) classification. Our results demonstrate that each CD4 epitopic density measured on circulating lymphocytes remains constant at a mean level of 46,000 epitopes per cell whatever the stage of the disease and whatever the serum p25 concentration. These data provide evidence that antibody accessibility to several CD4 epitopes is not altered by putative interactions between CD4 molecules and circulating virus, soluble gp120 or anti-CD4 autoantibodies. If such binding events, as expected, do occur in vivo, they are of too low a magnitude to influence the immunophenotyping. Furthermore, we show that mAb specific for different epitopes in the V1 and V2 domains of the CD4 molecule can be used interchangeably for the biological followup of the CD4+ cell population in blood samples of HIV-infected patients.

[Cytoplasmic immunoglobulins in chronic B-lymphoid leukemia]. / Immunoglobulines intracytoplasmiques et leucémie lymphoïde chronique B.

Chronic lymphocytic leukemia B-cells (B-CLL cells) have surface immunoglobulin (Smlg). In addition, cytoplasmic immunoglobulins (Clg) have been reported in chronic lymphocytic leukemia B-cells and are useful for ascertaining monoclonality of the disease. In a study of 60 cases of chronic lymphocytic leukemia B-cells, surface immunoglobulin determinations alone demonstrated monoclonality in 38% of cases, versus 65% of cases with combined surface immunoglobulin and cytoplasmic immunoglobulins determinations. Membrane markers were studied using a panel of monoclonal antibodies. Thirty-six per cent of patients were positive for CD 10. No correlations were seen between immunologic markers and clinical stage.

High-dose cytosine arabinoside and mitoxantrone in previously-treated acute leukemia patients.

35 patients with refractory or relapsed acute leukemia received salvage chemotherapy using high-dose cytosine arabinoside 2 g/m2 intravenously for 3 hours every 12 h, in 8 doses, followed by continuous infusion of mitoxantrone 12 mg/m2/day for 2 d. 9 patients had acute myeloblastic leukemia (AML), (4 relapsed, 5 refractory), 20 had acute lymphoblastic leukemia (ALL) (11 relapsed, 9 refractory) and 6 had chronic myelogenous leukemia (CML) in the blastic phase (BP). 4 out of 9 AML and 16 out of 20 ALL achieved complete remission. Median survival was 6 months for all patients and 10 months for responders. A short (1.5 months) chronic phase was achieved in 3 patients with CML. The main toxic effect was hematologic. A pharmacokinetic study was performed on mitoxantrone. No correlation was found with clinical response. The combination of mitoxantrone and ara-C is an effective antileukemic regimen, especially in ALL.