[Schnitzler syndrome]. / Le syndrome de Schnitzler.

This is the case report of a 57-year-old women with a 10-year long history of urticarial-like exanthema and monoclonal immunoglobulin M Kappa gammopathy, associated to arthralgia with pain of the lower limbs. A cutaneous biopsy and an inflammatory syndrome on laboratory testing helped to diagnose an urticarial vasculitis. A treatment with colchicine was set up but the response to therapy was not satisfactory. The diagnosis of Schnitzler syndrome was eventually suggested based on the combination of monoclonal gammopathy, urticarial and pain. A therapy with anakinra, an interleukin-1-receptor antagonist (IL-1), was started accordingly. The response was remarkable on skin rash, bone pain and laboratory testing including inflammatory syndrome.

Le cas présenté est celui d'une femme de 57 ans avec une histoire, longue de 10 ans, d'exanthème de type urticaire associé à des douleurs aux membres inférieurs et à une protéine monoclonale de type immunoglobuline M (IgM) Kappa. Une biopsie cutanée et un syndrome inflammatoire biologique ont permis de poser le diagnostic de vascularite mixte. La patiente est alors traitée par colchicine. Durant les années qui suivent, la colchicine n'a apaisé que modérément les plaintes. Un syndrome de Schnitzler est finalement évoqué face à la combinaison d'urticaire et de protéine monoclonale. Cette piste envisagée, un traitement par anakinra, un antagoniste des récepteurs de l'interleukine-1 (IL-1) est instauré, entraînant la disparition complète de l'urticaire.

[A trans-hospital pilot programme for onco-geriatry. The experience of the CHC-Liege]. / Programme pilote trans-hospitalier d'onco-gériatrie.

The authors offered to 296 consecutive cancer patients aged > or = 70 to undergo a joint comprehensive geriatric and oncological assessment. After pluridisciplinary discussion, several reflections have emerged: the need in 15 - 32% of cases to reinforce the role of the paramedical staff; the correlation between age, low clinical indices, alteration of renal function as well as geriatric characteristics; 67% of evaluated cases presented a significant geriatric profile; recommendations for patients' management in relation to their pattern of frailty and health aging (standard, adapted or palliative treatment).

Phase I - II study to assess the feasibility and activity of the triple combination of 5-fluorouracil/folinic acid, carboplatin and irinotecan (CPT-11) administered by chronomodulated infusion for the treatment of advanced colorectal cancer. Final report of the BE-1603 study.

Thirty-six metastatic colorectal cancer patients received every 2 weeks, as first- (17) or second-line (19) treatment a combined chronotherapy with CPT-11 (infused at day 1 from 2 to 8 a.m.; peak at 5 a.m.), given with 5FU (700 mg/m(2) per day; days 2-5) and folinic acid (300 mg/m(2) per day; days 2-5) both infused from 10 p.m. to 10 a.m. with a peak at 4 a.m., and carboplatin (40 mg/m(2) per day; days 2-5; infused from 10 a.m. to 10 p.m.; peak at 4 p.m.). The doses of CPT11 could be easily pushed from 120 to 180 mg/m(2) in successive cohorts in the phase I part of the study (11 cases). Twenty-five patients were then treated in the phase II of the trial. The overall toxicity was mild leading to dose-reductions in only 11-13% courses. The tumoral activity was interesting with 81% responses and 94% tumour control. Also prolonged survivals were recorded with 8.8 months of progression free and 15.6 months overall survivals. More prolonged survivals were observed in chemotherapy naive patients. Seven patients (19%) could be reoperated from their residual disease.

[Chronotherapy with 5-fluorouracil folinic acid and oxaliplatin delivered over 48 hours every second week in colorectal cancer. The CHC-Liège experience (Belgium)]. / Chronochimiothérapie à base de 5-fluorouracil, acide folinique et oxaliplatine administrée en deux jours toutes les deux semaines pour le cancer colorectal. L'expérience du CHC-Liège (Belgique).

One hundred and ten consecutive patients suffering from a colorectal cancer received chronotherapy infused over two days every two weeks. Each course comported 5 FU 3g/m(2), folinic acid (600 mg/m(2) - l. form or 1200 mg/m(2)--racemic form) and oxaliplatin (85/mg/m(2)--adjuvant indication or 100mg/m(2)--palliative indication). According to chronobiological concepts, 5 FU and folinic acid were infused from 10 pm to 10 am with a peak at 4 am while oxaliplatin was delivered from 10 am to 10 pm with a peak at 4 pm. The overall tolerance was excellent with a maximum of 17% patients experiencing a grade 3 toxicity. The toxicity was higher in women, in older patients (>=70) or in case of flat infusion. In adjuvant situation (60 cases), progression free and overall survivals established respectively at 76% (42+months) and 88% (45+months). Fifty-two percent response rate were recorded within the palliative group (50 cases) with an overall 68% disease control. Median progression free survival was seven months but median survival was not attained at 31+ months. Thirty percent patients could benefit from a curative surgery after chemotherapy. Older patients (>=70) experienced worsened survival. In conclusion, we think that our chrono-FOLFOX 2-12 should be proposed as standard treatment for colorectal cancer patients.

[Interest of chronotherapy in multidisciplinary management of oesophageal and gastric cancers]. / Intérêt de la chronothérapie dans le traitement pluridisciplinaire des cancers de l'oesophage et de l'estomac.

The authors evaluated the impact of a chronotherapy with 5-FU, folinic acid and carboplatine (chronomodulated infusions by ambulatory pumps; 5/21 days) for the management of oesophagus (52 cases) and gastric (56 cases) cancer patients. The overall tolerance of treatment was gauged excellent (grade 3-4; % patients: mucitis: 11-23%; leucopenia 6-19%; thrombopenia 18-50%; almost no digestive disturbances nor alopecia). Also tumor outcome was considered interesting with major responses rate in 61% (gastric) to 79% (oesophagus) of patients. The median survival of oesophageal cancer was limited to 9.2 months; the one of disseminated gastric cancer was 12.7 months but 72% of curatively resected patients were alive at 5+ years.

[Chronotherapy combining 5-fluorouracil, folinic acid and carboplatin as first line treatment in metastatic colorectal cancer. A phase 2 study]. / Chronothérapie associant le 5-fluorouracile, l'acide folinique, et le carboplatine en première ligne thérapeutique dans le cancer colorectal métastatique. Une étude de phase 2.

Seventy-two patients suffering from a metastatic colorectal cancer received, as first line treatment, a combination chronotherapy with 5-FU and folinic acid (infused from 10 pm to 10 am with a peak at 4 am, respectively at doses of 700 and 300 mg/m2 per day) and carboplatin (infused at the dose of 40 mg/m2 per day from 10 am to 10 pm with a peak at 4 pm). The courses of four days were repeated every two weeks. A major tumoral response was observed in 60% cases (68% in those not previously treated with adjuvant chemotherapy). The median times to progression and overall survival established at 11 and 27 months. The clinical (grades 3-4 in maximum 5% cases) and hematological (grades 3-4 in maximum 10-29% cases) toxicities were quite limited. Our observations suggest the interest to incorporate carboplatin in the combined infusional treatment of colorectal cancer.

[Feasibility survey (Phase I-II) of a four drugs combination (5-fluorouracil, folinic acid, carboplatin and irinotecan) delivered using a chronomodulated infusion in the treatment of advanced colorectal cancer]. / Etude de faisabilité (Phase I-II) d'une quadruple combinaison associant le 5-fluorouracile, l'acide folinique et le carboplatine à de l'irinotecan administrés en infusion chronomodulée pour le traitement du cancer colorectal avancé.

Seventeen colorectal cancer patients received as first (12 cases) or second line (5 cases) treatment a combined chronotherapy with CPT 11 (infused at day 1 from 2 to 8 am; peak at 5 am), given with 5 FU (700 mg/m2 per day ; days 2-5) and folinic acid (300 mg/m2 per day, days 2-5) both infused from 10 pm to 10 am with a peak at 4 am, and carboplatin (40 mg/m3/day - days 2-5 ; infused from 10 am to 10 pm - peak at 4 pm). The doses of CPT 11 could be easily increased from 120 up to 180 mg/m2 in successive cohorts of four patients through acceptable toxicity. Thus, five patients have already been treated in the phase II part of the trial. An interesting tumoral outcome has been observed: 88% major responses with no progression; median time to progression: nine months and median survival: 19.7 months.

[Adjuvant chemotherapy for Dukes B2 and C colon cancer combining 5-fluorouracil and folinic acid with or without carboplatin. Feasibility and comparison between standard and chronomodulated deliveries]. / Chimiothérapie adjuvante pour le cancer du colon de stades Dukes B2 et C comportant du 5-fluorouracile et de l'acide folinique, avec ou sans carboplatine. Faisabilité et comparaison d'une administration standard à une administration chronomodulée.

Thirty-seven patients operated from a Dukes B2-C colon cancer were randomised to receive as adjuvant infusional chemotherapy, nine 5 FU and folinic acid courses with or without carboplatin, as standard (de Gramont; 2 days every 2 weeks) or chronomodulated administration (4 days every 2 weeks). The overall tolerance was judged excellent with less than 7% courses with dose-adaptations. The two carboplatin arms presented an enhanced haematological toxicity, while some more cutaneous toxicity was observed in the chronomodulated arm with the three drugs.

Deletion of the 5'-ABL region: a recurrent anomaly detected by fluorescence in situ hybridization in about 10% of Philadelphia-positive chronic myeloid leukaemia patients.

Inclusion of the BCR-ABL ES probe in routine cytogenetics led to the identification of a subgroup of Philadelphia positive (Ph+) chronic myeloid leukaemia patients characterized by a 5'-ABL deletion. This anomaly was observed in 5/51 cases (9.8%). Cytological and clinical data suggest that the 5'-ABL deletion may be associated with dysplastic features of polymorphonuclear cells and metamyelocytes and a short chronic phase duration.

Successful mobilization of peripheral blood HPCs with G-CSF alone in patients failing to achieve sufficient numbers of CD34+ cells and/or CFU-GM with chemotherapy and G-CSF.

BACKGROUND: Mobilization with chemotherapy and G-CSF may result in poor peripheral blood HPC collection, yielding <2 x 10(6) CD34+ cells per kg or <10 x 10(4) CFU-GM per kg in leukapheresis procedures. The best mobilization strategy for oncology patients remains unclear. STUDY DESIGN AND METHODS: In 27 patients who met either the CD34 (n = 3) or CFU-GM (n = 2) criteria or both (n = 22), the results obtained with two successive strategies-that is, chemotherapy and G-CSF at 10 microg per kg (Group 1, n = 7) and G-CSF at 10 microg per kg alone (Group 2, n = 20) used for a second mobilization course-were retrospectively analyzed. The patients had non-Hodgkin's lymphoma (5), Hodgkin's disease (3), multiple myeloma (5), chronic myeloid leukemia (1), acute myeloid leukemia (1), breast cancer (6), or other solid tumors (6). Previous therapy consisted of 10 (1-31) cycles of chemotherapy with additional chlorambucil (n = 3), interferon (n = 3), and radiotherapy (n = 7). RESULTS: The second collection was undertaken a median of 35 days after the first one. In Group 1, the results of the two mobilizations were identical. In Group 2, the number of CD34+ cells per kg per apheresis (0.17 [0.02-0.45] vs. 0.44 [0.11-0.45], p = 0. 00002), as well as the number of CFU-GM (0.88 [0.00-13.37] vs. 4.19 [0.96-21.61], p = 0.00003), BFU-E (0.83 [0.00-12.72] vs. 8.81 [1. 38-32.51], p = 0.00001), and CFU-MIX (0.10 [0.00-1.70] vs. 0.56 [0. 00-2.64], p = 0.001134) were significantly higher in the second peripheral blood HPC collection. However, yields per apheresis during the second collection did not significantly differ in the two groups. Six patients in Group 1 and 18 in Group 2 underwent transplantation, and all but one achieved engraftment, with a median of 15 versus 12 days to 1,000 neutrophils (NS), 22 versus 16 days to 1 percent reticulocytes (NS), and 26 versus 26 days to 20,000 platelets (NS), respectively. However, platelet engraftment was particularly delayed in many patients. CONCLUSION: G-CSF at 10 microg per kg alone may constitute a valid alternative to chemotherapy and G-CSF to obtain adequate numbers of peripheral blood HPCs in patients who previously failed to achieve mobilization with chemotherapy and G-CSF. This strategy should be tested in prospective randomized trials.

[Clinical case of the month. Metastatic endocarditis: clinical observation and review of the literature]. / Le cas clinique du mois. L'endocardite métastatique: observation clinique et revue de la littérature.

The authors describe a case of metastatic endocarditis associated with a gastric carcinoma. The diagnosis was made early and the treatment by surgery and chemotherapy allowed a survival of 18 months, which is unusually long. The differential diagnosis is discussed and includes nonbacterial thrombotic endocarditis, infectious endocarditis and primary tumors of the heart.

Ambulatory chrono-chemotherapy by portable pumps: feasibility and compliance. Nursing aspects.

A study was undertaken among thirty seven advanced cancer patients, receiving chronochemotherapy by ambulatory programmable-in-time pumps. Drugs were infused through simple or double chamber venous, and/or arterial totally implantable side-ports. The aim was to evaluate the treatment feasibility in an ambulatory mode, while appreciating the patient's physical and psychological tolerance and measuring the treatment's impact on the patient's daily life and family unit. The results of the study showed that, out of a total of 1613 days of treatment, only 27 returns to the hospital were required, which were due to minor incidents (mainly pipe leaks). No treatment was abandoned or interrupted by non-compliance and all patients maintained the ambulatory mode of treatment. Moreover patients cooperated fully with this mode of treatment with firm support from their relatives. The study emphasized the necessity of proper training for patients and good information about the delivery system, as a means of preventing the poor functioning of equipment and the ability to take promp action in order to maintain life functions and to confront potential side effects.

Levamisole adds granulocyte toxicity to 5FU-based chemotherapies in adjuvant treatment of Dukes B-C colorectal cancer. A preliminary report.

41 patients (pilot study-I) and 50 patients (multicenter study II) were randomized to receive as systemic chemotherapy for 6 courses with 5 FU alone (A) [440 (I)-450 (II) mg/m2 IV bolus, 5/21 days] or folinic acid followed by 5 FU (B) (respectively 200 and 370 mg/m2 IV bolus, 5/21 days). In the multicenter trial, oral levamisole at the dose of 150 mg/day (3/14 days) was added to chemotherapy for one year. Ten patients in study I and 19 patients in study II also received a post-operative course of intra-portal chemotherapy. Toxicity was evaluated respectively on 232 (I) and 276 (II) courses. Clinical limiting toxicities were stomatitis and diarrhea. In protocol II, a significant enhancement of grades 3-4 granulocyte toxicity was seen (17.3% of courses in II vs only 3.4% in I; p < 0.001). This was especially recorded in the group treated with 5-FU alone (26% of courses in A vs 11% in B; p < 0.001). Levamisole was therefore stopped in 12 cases (10 cases in A; 2 cases in B).

Pregnancy occurring during complete cytogenetic response after interferon therapy in chronic myeloid leukaemia.

A 25 year old woman with chronic myelogenous leukaemia was treated for 27 months with alpha-interferon, leading to complete haematological and cytogenetic remission. One year after interruption of treatment, she became pregnant and delivered a healthy full term infant. This case provides further evidence in support of the safety of alpha-interferon with respect to the fertility of women of childbearing age.

Dose-response relationship of epirubicin-based first-line chemotherapy for advanced breast cancer: a prospective randomized trial.

PURPOSE: We compared prospectively the antitumor efficacy of two combination chemotherapy regimens with two different dose levels of epirubicin as first-line treatment for advanced breast cancer. PATIENTS AND METHODS: One hundred forty-one fully assessable patients were randomized to receive either our intensified schedule (group A, n = 71) of epirubicin 50 mg/m2 on days 1 and 8 (every 3 weeks), or a non-intensified program (group B, n = 70) in which epirubicin was only administered on day 1. Both groups also received fluorouracil (5 FU) and cyclophosphamide 500 mg/m2 on day 1 of each course. RESULTS: A statistically significant difference in response rate was observed (69% in group A v 41% in group B, P < .001) for both locally advanced (LA) and recurrent metastatic (RM) disease. Response duration (22 v 14 months, P < .01) and time to progression (TTP; 19 v 8 months, P < .02) were also significantly improved. Overall survival was similar in both groups. However, univariate and/or multivariate analyses showed a meaningful relationship between type of treatment allocated, dose-intensity (DI) of epirubicin, and response rate, as well as between TTP and survival. Ultimately, TTP and survival were also influenced by further treatment modalities, namely, hormonotherapy and chemotherapy. CONCLUSION: This study validates prospectively the concept of a dose-response relationship for an anthracycline-based chemotherapy in previously untreated advanced breast cancer.

[Tolerance of adjuvant treatment combining postoperative intraportal chemotherapy and a systemic treatment based on 5-fluorouracil in colorectal carcinoma with a histologically poor prognosis]. / Tolérance d'un traitement adjuvant associant une chimiothérapie intraportale post-opératoire et un traitement systémique à base de 5-Fluorouracil dans les carcinomes colorectaux de stades histopronostiques défavorables.

From April 89 to October 90, 41 patients operated for a Dukes B or C colorectal cancer were randomized to receive 6 courses of adjuvant treatment with (A) 5-FU alone (440 mg/m2 IV bolus 5/21 days) or (B) folinic acid (200 mg/m2 IV bolus 5/21 days) preceding 5-FU (370 mg/m2 in short infusion 5/21 days). Ten patients received also one course of immediate post-operative continuous portal infusion (5-FU 500 mg/m2/day x 7 followed by a 2 hours infusion of mitomycin C 10 mg/m2). The portal treatment was well tolerated (1 case of GI tract disturbances, 1 catheter obstruction). The toxicity of adjuvant systemic treatment was evaluated on 232 courses (125 A, 107 B). Hematologic and skin toxicities, alopecia and nausea-vomiting were mild. The limiting toxicities (expressed as percentages of courses) were stomatitis (grades 2-3: 11.4% A; 22.6% B) and diarrhea (grades 3-4: 7.3% A; 14.2% B; one toxic death was to deplore in arm B from a grade 4 diarrhea). The pilot study has demonstrated the feasibility of the adjuvant treatment proposed; a multicentric randomized trial (expected accrual: 800 patients) has therefore been activated on 11.01.90; all patients will also receive levamisole while radio-therapy will be mandatory for rectal cancer.