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Aim: Physical or psychological well-being is an essential component of quality care assessment in palliative unit. This assessment is mainly based on self-assessment (questionnaires or interviews). The aim of this study is to compare the clinical characteristics of patients able to fulfill a questionnaire and those not able to do that., Methods: The clinical characteristics of 166 cancer patients admitted in palliative care unit from December 2006 to February 2008 have been collected. Characteristics of patients able to fulfill a questionnaire (80, 48.2%) have been compared to other patients (86, 51.8%). Moreover, functional independence measure (FIM) had been evaluated by nurses., Results: Median age (60 versus 62) and sex ratio (40/40 versus 42/44) are similar in both groups. Lung primaries are significantly less frequent in patients able to fulfill the questionnaire (4% versus 17%, P=0.005). Patients able to fulfill the questionnaire had had better performance status (Karnofsky Index≤30%: 54% versus 21%, P<0.0001). The total score of FIM (56.0 versus 91.5, P<0.00001) and the median overall survivals (2.3 weeks versus 6.6 weeks, P=0.0001) were significantly lower in the group of patients non able to fulfill the questionnaire., Conclusions: Patients able to fulfill a questionnaire represent only 48.2% of all consecutive admitted patients. These patients are not representative of all patients since they had better performance status, they are less dependent and they display significant better survival. We have to think about new methods to avoid the biases generated by the use of patient-reported outcomes., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Chemotherapy for the treatment of early-stage breast cancer (ESBC) patients improves survival outcomes. However, its most common acute toxicity is myelosuppression, which can reduce the delivered dose and compromise the survival benefit. Because FEC100-docetaxel (FEC100-D) is a common protocol for ESBC, we evaluated its febrile neutropenia (FN) incidence and the role of its hematological toxicity on the individual relative dose-intensity (RDI)., Patients and Methods: It is a French single-center, observational, retrospective study. Patients received adjuvant/neoadjuvant FEC100-D treatment, without primary prophylaxis by granulocyte colony-stimulating factors (G-CSF). The neutrophil count the day before the planned chemotherapy cycle had to be over 1,500.mm(-3) for the treatment to be administered. Data collected included: date and dose of chemotherapy cycles, FN and high grade of hematological toxicity occurrence for each course, G-CSF prescription., Results: One thousand, seven hundred and fifty-seven cycles in 284 patients were delivered. FN was observed in 4.9% (n = 14) of the patients, without hospitalizations or deaths after. Grade 3-4 neutropenia occurred in 5.8% of the cycles, during the first cycle in 40% of cases. Seventeen percent of our patients received less than 85% of RDI., Conclusion: The hematotoxicity of this treatment is acceptable. The risk of FN is low. No G-CSF primary prophylaxis is needed without additional risk factor.

As part of a study in the North of France for screening pelvic tumours with plasma proteomic analysis, we included 82 women with hereditary risk of ovarian cancer. We report here the consequences of organized screening with usual tests. CA 125 sampling and a transvaginal pelvic ultrasound by a radiologist were systematically conducted every 6 months. Seventy-two patients were eventually evaluable. Two incident cases of peritoneal carcinomatosis (FIGO IIIB, malignant epithelial serous high-grade tumors) were discovered in two asymptomatic women with a deleterous BRCA1 mutation (2.7%). We did not observe any other primary cancer cases but an ovarian metastasis of a breast cancer. Forty women went off the study: 32 had a prophylactic bilateral salpingo-oophorectomy. Consistent with the literature, biannual screening tests combining CA125 and pelvis ultrasound is ineffective for early detection of a pelvic tumor of tubal or ovarian origin. Testing for BRCA1 or BRCA2 deleterious mutations is then crucial for suspected family syndromes of breast and ovarian cancer. For women carrying a deleterous mutation on BRCA1/2 a salpingo-oophorectomy is the only way, only the time of this surgery is debatable.

We propose here a general review of current questions related to early trials, including the choice of the primary endpoint, role of bayesian designs, role of stratification and randomization for phase 2 trials, patient selection, and new designs for phase 1 and phase 0 trials. We also discuss the difficulties to apply such methodologies to molecular targeted therapies development.

The development of molecular targeted therapies requires some specific methodological approaches. Dose-limiting toxicities are rare in phase I studies the maximal tolerated dose is rarely established. On the contrary, the biological active dose is often determined as the dose inducing biological effect on the target without significant clinical toxicity. Several designs of phase II are described (selection phase II, randomized phase II, stratified phase II...). All of them are indicated in specific situations. The discontinuation treatment studies and the validation of biomarkers (as surrogate endpoints or as classifiers) are the two main particularities of phase III studies designed for the assessment of molecular targeted therapies.

Use of antibiotic prophylaxis (AP) in clean breast cancer surgery is still controversial. We assessed the efficacy of preoperative AP in a prospective study of 171 clean breast cancer procedures following previous anticancer chemotherapy. From June 1998 to July 2001, we analyzed 171 procedures. In 133 cases. AB with cefuroxime was performed. Wound infection rate was 3 out of 171 procedures (WI rate of 2/131 with AP compared with 1/37 without AP, p = 1.0). This study suggests that AP is not systematically required in breast cancer surgery following previous anticancer chemotherapy.

Background: Surgery followed by irradiation is considered to be the standard treatment but require frequently a total laryngectomy. Chemotherapy followed by irradiation is available in larynx and hypopharynx squamous cell carcinoma (SCC) treatment. Are results obtained in daily induction chemotherapy usefulness identical to results obtained in larynx preservation studies?, Patients and Method: We conducted a retrospective study on patients treated at centre Oscar-Lambret, Lille, from 1986 to 1995, by chemotherapy followed by definitive radiotherapy or by surgery and radiotherapy for laryngeal or hypopharyngeal cancer treatment. All patients were naive of previous head and neck SCC and a surgical treatment, requiring total laryngectomy, should be proposed with curative intent. Induction chemotherapy associated cisplatin (100 mg/m2) on day 1 and 5-fluorouracil (5FU)(1,000 mg/m2) on days 1-4 or 1-5. Irradiation was performed for responders (complete or partial > 50%). If case of non-responder, patients underwent surgical treatment followed by irradiation. We compared results obtained with patients enrolled in clinical trial and with patients whom benefited from this protocol out of trial., Results: Hundred-eight patients were evaluable for purposes of this study. Fifty-two patients were included in clinical trial (group 1) while 56 patients (group 2) were not. There was no statistical difference as regard neither to sex nor to node (palpable or not palpable) and metastasis status between the groups. We found a higher frequency of laryngeal tumour in group 2 (31 vs 17; p =.03). We observed more stage III and less stage IV in group 1. For chemotherapy-related toxic reactions, the exclusive statistical difference observed was haematological toxicity grade III and IV after the second cycle (0 pt in group 1 vs 8 pts in group 2; p =.02). After initial treatment, complete response was achieved without statistical difference between the groups (88.2% vs 78%; p =.27). A surgical procedure was performed in 46 cases without difference according to the reference group and functional larynx preservation was 55.8% (29/52) in group 1 and 53.6% (30/56) in group 2. Whatever the group, causes of death were similarly distributed. Cancer was the first cause of death in both groups. The overall survival of the population (108 patients) was 81.5% at one year, 49.6% at 3 years and 35.3% at 5 years with a median survival of 3 years. There was no statistical difference between both groups. Some parameters influenced the overall survival like T (p =.04), response to chemotherapy (p=.006), extra capsular spread (p = 0.03) and response after completion treatment., Conclusion: Induction chemotherapy is available for larynx preservation but cannot be considered as a standard treatment. Nevertheless, results should be reproduced in daily practice with experimented teams as found with non included patient's results. The long-term side effects of such protocols should be evaluated. Recent publication, on increase postoperative infection after chemotherapy, should be evaluated in clinical trial. If confirmed, cost effectiveness of such complication must be integrated in larynx preservation protocols. Larynx preservation remains an interesting point of view for patients but stay an optional procedure and not a reference.

Some patients underwent laparoscopy without optimal debulking surgery as initial treatment for advanced ovarian carcinoma. The amount of residual tumor following primary surgery was an important prognosis factor. Neoadjuvant chemotherapy is a new therapeutic approach. Secondary, optimal surgery could be done in better conditions. The purpose was to access the ability of preoperative abdominopelvic CT to predict success of debulking surgery for ovarian carcinoma: less than 1 cm of residual tumor size after initial surgery. We reviewed 39 patients (2 stages Ic, 1 stage IIc, 22 stages III and 14 stages IV) operated on for ovarian carcinoma between January 1992 and December 1997. Surgical criteria of inability to perform optimal surgical cytoreduction were compared with abdominopelvic CT done the month before. CT scans were prospectively assessed by radiologist A and retrospectively (3 months to 6 years delay) rewiewed separately by radiologists A and B without surgical data. Nineteen patients underwent optimal debulking surgery: 13 no residual tumor and 6 with residual lesions under 1 cm. The interreader (0.73) and intrareader (0.9) agreement, worked out by Kappa coefficient, was juged good to very good. The sensitivity of CT was 91% with a specificity of 95%. These results allowed us to determine wich CT criteria were accurate and reproducible to be a helpfull for therapeutic choice and to avoid laparotomy without optimal surgery.

It is a randomised cross-over multicenter study comparing the efficacy and the tolerance of granisetron (Gra) 1 mg and ondansetron (Ond) 8 mg, oral, given during two consecutive cycles to 188 naive patients scheduled to receive a moderately emetogenic chemotherapy. The antiemetic treatment is given one day per course, 1 hour before chemotherapy and the second administration from 8 to 12 hours after the beginning, during each of the two cycles; alternatively according to the randomisation. Five criteria are assessed; nausea (ordinal and visual analogic scales), emeric episodes (vomiting orland retching), complete response (minor or no nausea, no emetic episode and no rescue treatment), patient preference and tolerance. The intent to treat analysis showed no significant difference at cycle 1 between Gra and Ond; at cycle 2, there is no significant difference in the number of emetic episodes; for the prevention of nausea, the ordinal scale shows a significant difference (p = 0.028 in favour of Gra at day 1 (D1) but not from D2 to D5. Gra induced more complete response than Ond at D1 (p = 0.028), but not from D2 to D5. The cross-over study did not show any period or order effect, whereas a treatment effect on Ond was significant in favour of Gra (p = 0.01). There is no significant patients preference in favour of Gra or Ond. In conclusion, Gra was more efficient in preventing nausea and obtaining complete response on the first day of treatment, significantly at the second cycle. Both Gra and Ond had a good antiemetic activity for moderately emetogenic chemotherapy with complete response rates always over 50% on day 1; delayed emesis remain less weli controlled.

The aim of this study was to determine the value of haematological counts at the 4th day of a chemotherapy cycle, in order to foresee neutro and/or thrombocytopenia during the same chemotherapy cycle. One hundred and ten cycles of chemotherapeutic regimens with carboplatin (400 mg/m2, dl) and 5-fluorouracile (1 g/m2/d, by iv continuous infusion for 96 hours) every 3 weeks, were analyzed for 42 patients with locally advanced but non metastatic squamous cell carcinoma of head and neck, without prior chemotherapy. Lymphocyte counts were significantly decreased at the 4th day but normalized at the 8th day (P < 10(-6)). Decreases of lymphocyte and neutrophil counts at the 4th day were significantly correlated to grade > 2 neutropenia. The positive predictive value of lymphocyte or neutrophil counts is about 50% for some cut-off values but not high enough, with the schedule of chemotherapy in our study, to justify the systematic prophylactic therapy with haematopoietic growth factors.

We performed a retrospective analysis on all head and neck cancers with hypercalcemia seen between January 1988 and June 1993 at the Centre Oscar-Lambret, cancer center of northern France. Hypercalcemia, non albumin-corrected, higher than 2.60 mmol/l was observed in 173 of 3,394 consecutive patients (5%). Median age of patients with hypercalcemia was 53 years and 97% of these patients were males. All patients with hypercalcemia had advanced or recurrent and/or metastatic squamous cell carcinoma of head and neck (SCCHN); 31 of them were not pretreated. There was no significant difference in histology between patients with or without hypercalcemia, but hypercalcemia was most commonly associated with lesions of the oropharynx (p = 0.00001). The median of calcemia was of 2.83 mmol/l (2.61-4.70). Gastrointestinal and neurologic symptoms respectively occurred in 24% and in 14% of patients and bone metastases in 25% of patients. Median survival after the first determination of hypercalcemia was of 7 weeks (0-128) for the overall group of 173 patients and of 12 weeks (1-128) for those 31 patients with hypercalcemia at initial diagnosis. Prognosis associated factors were: efficacy of antitumour treatment, performance status and hypercalcemia superior or not to 3 mmol/l. We concluded that hypercalcemia in head and neck cancer is usually a late manifestation associated with advanced, recurrent and/or metastatic disease and carries a poor prognosis. The prolongation of survival can be obtained in some patients if an effective antitumour treatment is feasible.

Plasma levels of cholesterol, HDL cholesterol (HDL chol), LDL cholesterol (LDL chol), triglycerides, Al apoprotein and B apoprotein were studied in 73 patients receiving 500 mg aminoglutethimide (AG)/day and 40 mg hydrocortisone/day for advanced breast cancer. These dosages were done before treatment and then repeated during AG therapy. When all patients were considered together, a significant increase of cholesterol, HDL chol, LDL chol and Al apoprotein was noted. If one considers two groups of patients: group A (where cholesterol and triglycerides plasma levels were normal before treatment) and group B (where cholesterol and/or triglycerides plasma levels were high before treatment), it appears that variations differ in both groups. In group A patients we found an increase in cholesterol, chol LDL, B apoprotein and to a lesser extent Al apoprotein plasma levels. In group B patients there was an increase in cholesterol, HDL chol and Al apoprotein plasma levels.

Tumour tissue levels of platinum were determined in patients with head and neck tumours receiving carboplatin (11 patients, 400 mg/m2) and iproplatin (5 patients, 360 mg/m2). The platinum concentrations ranged from 1.1 +/- 0.4 ng Pt/mg tissue (iproplatin administration) to 1.4 +/- 0.3 ng Pt/mg tissue (carboplatin administration). These results were compared with published platinum levels after cisplatin administration. Although the administered dose of carboplatin (1.08 mmol/m2) and iproplatin (0.86 mmol/m2) was higher than the cisplatin one (0.33 mmol/m2), no significant statistical differences were observed in the resulting platinum tissue levels. The constancy of tumour platinum level after treatment with different platinum complexes could be explained, at least for carboplatin and cisplatin, by both the tumour diffusion properties and the reactivity of the drugs.