Phase II trial of mapatumumab, a fully human agonistic monoclonal antibody that targets and activates the tumour necrosis factor apoptosis-inducing ligand receptor-1 (TRAIL-R1), in patients with refractory colorectal cancer.

BACKGROUND: Recombinant tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces tumour-selective apoptosis in various pre-clinical models by binding its specific receptors expressed on cancer cells. Mapatumumab is a fully human monoclonal antibody that is agonistic to the TRAIL Receptor 1 (TRAIL-R1). METHODS: This phase II multicentre study was designed to evaluate the efficacy and safety of mapatumumab in patients with colorectal cancer (CRC) who had failed to respond to, were intolerant to, or not candidates for fluoropyrimidine, oxaliplatin, and irinotecan-based regimens. All patients received two loading doses of mapatumumab (20 mg kg(-1) every 14 days), followed by maintenance therapy with 10 mg kg(-1) infused every 14 days. RESULTS: A total of 38 patients, who had progressive disease after a median of three earlier chemotherapy lines, were enrolled. No response according to the Response Evaluation Criteria in Solid Tumors was observed. A total of 12 patients (32%) achieved stable disease for a median of 2.6 months. The median progression-free survival was 1.2 months. The most common adverse events reported, regardless of relationship, were fatigue, nausea, anorexia, and abdominal pain. Plasma mapatumumab concentrations were within the range of exposures predicted by the results of phase I studies of mapatumumab. CONCLUSION: No clinical activity of single-agent mapatumumab was observed in patients with advanced refractory CRC. However, on the basis of its favourable safety profile and pre-clinical evidence of potential synergy in combination with agents commonly used in the treatment of colorectal cancer, further evaluation of mapatumumab in combination with chemotherapy is warranted.

Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial.

BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer (NSCLC). This phase III study of chemotherapy-naïve advanced NSCLC patients was designed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination. Paclitaxel was given at a dose of 200 mg/m(2) (3-h intravenous infusion) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2), all repeated every 3 weeks. Survival, toxicity and quality of life were also compared. PATIENTS AND METHODS: Patients were randomised to receive one of the two combinations, stratified according to centre, performance status, disease stage and histology. The primary analyses of response rate and survival were carried out on response-evaluable patients. Survival was also analysed for all randomised patients. Toxicity analyses were carried out on all treated patients. RESULTS: A total of 618 patients were randomised. The two treatment arms were well balanced with regard to gender (83% male), age (median 58 years), performance status (83% ECOG 0-1), stage (68% IV, 32% IIIB) and histology (38% squamous cell carcinoma). In the paclitaxel/carboplatin arm, 306 patients received a total of 1311 courses (median four courses, range 1-10 courses) while in the paclitaxel/cisplatin arm, 302 patients received a total of 1321 courses (median four courses, range 1-10 courses). In only 76% of courses, carboplatin was administered as planned at an AUC of 6, while in 96% of courses, cisplatin was given at the planned dose of 80 mg/m(2). The response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively. Excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms. CONCLUSIONS: This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC. Although paclitaxel/carboplatin yielded a similar response rate, the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option.

The utilization and efficiency of the informal caregivers' coping strategies.

This study highlights the coping strategies used by informal caregivers whose husbands live with cancer. It also aims at measuring the efficiency of the selected strategies. The convenience sample was composed of 30 informal caregivers. The results indicate that informal caregivers primarily use support, optimism, independence, and facing of the situation. In general, the categories of coping strategies most often used by informal caregivers are considered by them to be the most efficient. The results of the study encourage nurses to identify more regularly the coping strategies used by informal caregivers; to recognize their efficiency and implement interventions likely to improve the informal caregivers' stress management.

Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer.

BACKGROUND: In phase II trials, paclitaxel has been shown to have antitumor activity in patients with advanced non-small-cell lung cancer (NSCLC). However, the survival and quality-of-life (QOL) benefits of paclitaxel used as a single agent compared with supportive care alone have not been assessed in a randomized clinical trial. METHODS: A total of 157 patients with stage IIIB or IV NSCLC who had received no prior chemotherapy were randomly assigned to receive either best supportive care alone (78 patients) or paclitaxel plus supportive care (79 patients). Paclitaxel was administered as a 3-hour intravenous infusion every 3 weeks. Supportive care included palliative radiotherapy and supportive therapy with corticosteroids, antibiotics, analgesics, antiemetics, transfusions, and other symptomatic therapy as required. The primary end point of the study was survival. Time to disease progression, response rate, adverse events, and QOL were secondary end points. RESULTS: Pretreatment characteristics were evenly distributed between the two arms. Survival was statistically significantly better in the paclitaxel plus supportive care arm than in the supportive care alone arm (two-sided P =.037) (median survival = 6.8 months versus 4.8 months). Cox multivariate analysis showed paclitaxel plus supportive care to be statistically significantly associated with improved survival (two-sided P =.048). QOL was similar for both treatment arms, except for the functional activity score of the Rotterdam Symptom Checklist, where QOL data statistically significantly favored the paclitaxel plus supportive care arm (two-sided P =.043). CONCLUSION: The addition of paclitaxel to best supportive care significantly improved survival and time to disease progression compared with best supportive care in patients with advanced NSCLC and may improve some aspects of QOL.

A phase II trial of mitomycin, ifosfamide and cisplatin in recurrent carcinoma of the cervix.

The purpose of this study was to evaluate the efficacy and the toxicity of mitomycin, ifosfamide, and cisplatin in patients with recurrent carcinoma of the cervix. Between July 1992 and March 1995, 20 patients with recurrent cervical cancer were enrolled in this study. No patients had received prior chemotherapy for metastatic disease, except some were exposed to cisplatin as a radiosensitizer at the time of their diagnosis. Mitomycin-C 6 mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2 were given intravenously every 3 weeks. All patients were assessible for response and toxicity, and none was lost to follow-up. All patients except one had squamous cell carcinoma. The overall response rate was 45% (2 complete remissions and 7 partial remissions). The mean response duration was 35 months, and the median survival from treatment for the whole group was 14 months. Fifteen percent of all cycles produced grade 3 or 4 myelosuppression, and the main nonhematologic toxicity was nausea and vomiting, which was reported in 11.5% of all cycles. One death occurred secondary to chemotherapy-induced septicemia. Three patients are still alive, two with a complete response and one with a partial response. In conclusion, mitomycin, ifosfamide, and cisplatin have a good activity in recurrent carcinoma of the cervix and are comparable to other combination chemotherapy.

Description of the caregiver's educational needs and the degree of her dissatisfaction.

This study emphasized the learning needs of caregivers whose husbands have cancer and describes their level of dissatisfaction concerning these needs. A convenience sample of 30 women caregivers was used. The results demonstrate that caregivers possess initial acquired knowledge as learners and have 26 specific learning needs. The existence of a learning need produces a level of dissatisfaction among the female caregivers. Among these learning needs, the most likely to generate the greatest dissatisfaction are the learning needs associated with personal concerns. The results encourage nurses to play a more active role in learning by assessing whether the information the caregivers are receiving is understood well enough to meet their learning needs.

A phase I trial of high-dose paclitaxel, cyclophosphamide and mitoxantrone with autologous blood stem cell support for the treatment of metastatic breast cancer.

The aim of this phase I study was to determine the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and efficacy of a new combination of cyclophosphamide (6 g/m2), mitoxantrone (70 mg/m2), with dose escalation of paclitaxel (TaxolR) at a starting dose of 250 mg/m2 given intravenously over 3 h in a transplantation setting. Patients with metastatic breast cancer and chemosensitive disease were eligible. The autologous blood stem cell re-infusion and subsequent recovery occurred in an out-patient setting. 50 patients were enrolled, but 10 withdrew. 40 completed the entire protocol. At 400 mg/m2 paclitaxel administered over 3 h, 3 of 6 patients experienced serious adverse events: approximately 20-40 min after completion of infusion, diaphoresis, bradycardia mild hypotension and diarrhoea occurred; 2 patients lost consciousness for a few minutes. An extended infusion schedule delivering 400 mg/m2 paclitaxel over 6 h rather than 3 h was initiated at this level without patients experiencing this DLT. At the next dose of 450 mg/m2 paclitaxel over 6 h, the same DLT was seen as at 400 mg/m2 paclitaxel over 3 h and, therefore, MTD was reached. Time to recovery for the absolute neutrophil count > or = 0.5 x 10(9)/l was 10-19 days (median 12 days); and for platelets > or = 20 x 10(9)/l was 18-20 days (median 11.5 days). 21 patients developed neutropenic fever that required intravenous antibiotics and re-admission; the transfusion frequency for packed red blood cell was 0-5 units (median 2 units) and for platelets, 1-5 encounters (median 2). 13 complete responses, 1 patient with no evidence of disease and 19 partial remissions were documented. The dose of 400 mg/m2 at an infusion rate of 6 h will be used for the ongoing phase II study to evaluate efficacy and toxicity further.

Translation, adaptation and validation process for the DINA instrument. Derdiarian Information Needs Assessment.

This article presents an adapted and validated version of the Derdiarian Information Needs Assessment (DINA) instrument. This French adaptation of the DINA instrument helps to determine the learning needs of the caregiver whose spouse is a cancer patient. The design of the original DINA instrument is explained. The accuracy of the statements comprising the adapted instrument was established by agreement by two language experts about the phrasing of each question. Using a conceptual analysis of the term "learning need" and a perceptual approach, modifications were made to the DINA instrument. Measuring attributes appropriate for this instrument are indicated. The article puts forward the validity and reliability of the French adaptation of the instrument. It concludes with stressing the usefulness of this instrument for the nursing practice.

In vitro carboplatin-mesna interaction in aqueous solution, human plasma and urine.

The chemotherapeutic benefit of synergistic drug combinations and higher drug dosages has generated interest in the application of these regimens to cancer patients. A major obstacle in the application of these strategies to the treatment of cancer is the dose-limiting toxicities of drug combinations. Sodium 2-mercaptoethane-sulfonate (mesna), a chemoprotective drug, may reduce the nephrotoxicity of carboplatin [CBDCA, paraplatin, JM-8, cis-diammine (1,1-cyclobutane dicarboxylato) platinum II] when administered in combination chemotherapy. The purpose of this study was to evaluate, compare and contrast in vitro the interaction of mesna with carboplatin in aqueous solution, human plasma and urine. Carboplatin and mesna were incubated separately and together at clinically relevant concentrations in plasma and urine. The concentration of carboplatin was assayed by HPLC, and the decay of carboplatin alone and in combination with mesna was compared. The incubation of carboplatin with mesna in human plasma up to 8 days did not result in a statistically significant interaction: the half-life of carboplatin in plasma when it was combined with mesna was 1.62 +/- 0.08 (SE) days compared to 1.85+/- 0.04 (SE) days for carboplatin by itself. The incubation of drugs in fresh human urine up to 15 days gave a half-life of 3.43+/- 0.8 (SE) days for carboplatin alone and 2.78 +/- 0.7 (SE) days for carboplatin when it was combined with mesna. Our results show that carboplatin and mesna do not significantly interact in plasma. Although a statistically significant difference between the half-life of carboplatin and the half-life of the carboplatin/mesna combination is detected in urine, it is not likely to be clinically significant, as there is no significant interaction detected in the first 48 h). It is thus unlikely that mesna would substantially affect the pharmacokinetics of carboplatin when both are given together to patients as part of combination chemotherapy regimens.

Remission induction therapy of untreated acute myeloid leukemia using a non-cytarabine-containing regimen of idarubicin, etoposide, and carboplatin.

BACKGROUND: The safety and efficacy of idarubicin, etoposide, and carboplatin as remission induction therapy for patients younger than 60 years with untreated acute myeloid leukemia was studied as an alternative to standard regimens based on cytarabine plus anthracycline. METHODS: Eligible patients received idarubicin (36-40 mg/m2), etoposide (500 mg/m2), and carboplatin (1000-1500 mg/m2) over 5 days. Those who achieved complete remission received a single course of cytarabine 1.5 gm/m2 every 12 hours for a total of 12 doses. D-xylose absorption was studied as a marker for cytotoxic therapy-induced gut mucosal damage. Cytogenetic and immunophenotyping studies were performed at the time of diagnosis and examined for prognostic importance. RESULTS: Remission was achieved in 29 (67%) of 43 patients with a single induction course. The median leukemia free and overall survival times were 15.4 months (95% CI 6.5-24.2) and 12.5 months (95% CI 5.9-19.1), respectively. Induction mortality was 14%. Karyotype (normal, simple, or complex vs. very complex) was the strongest predictor of remission (79% vs. 25%, P=0.01), leukemia free survival (odds ratio [OR] 19.3, 95% CI 2.7-138.9), and overall survival (OR 5.4, 95% CI 2.1-13.9). Dose-limiting gut mucosal toxicity was greatest during Weeks 2 and 3. Bloodstream infections occurred in 49% of patients at a median of 12 days. Grade 3-4 diarrhea, nausea, stomatitis, esophagitis/dysphagia, and vomiting developed in 33%, 26%, 23%, 9%, and 2% of cases, respectively, at a median of 17, 16, 11, 15.5, and 21 days, respectively. CONCLUSIONS: This regimen was active in adults younger than 60 years with untreated acute myeloid leukemia and normal, simple, or complex karyotypes. Remission duration was confounded by karyotype. Mucosal toxicity limited the tolerability of this regimen. These adverse effects might be overcome by increasing the intensity of postremission therapy and modifying the dosing schedule.

Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study.

PURPOSE: To evaluate the effect of megestrol acetate at a lower dose than previously investigated on the symptoms of cachexia in patients with advanced cancer. METHODS: A total of 84 patients with advanced, solid tumours not responsive to hormone therapy were enrolled in this double-blind, crossover study. During phase 1, patients were randomly assigned to receive megestrol acetate (160 mg 3 times daily) for 10 days or placebo. During phase 2, after a 2-day washout period, patients received the alternate treatment for 10 days. Patients underwent daily assessments of activity, nausea, appetite and well-being by means of a visual analogue scale (VAS). In addition, nutritional status (weight, tricep skinfold measure, arm muscle circumference), energy intake, fatigue (Piper Fatigue Scale) and quality of life (Functional Living Index-Cancer [FLIC]) were assessed. RESULTS: Among the 53 evaluable patients megestrol acetate resulted in a significant improvement in appetite (p = 0.005), activity (p = 0.007) and well-being (p = 0.03). There was no significant change in the intensity of nausea, nutritional parameters, energy intake or FLIC scores. There was a significant improvement in 2 of the 3 factors measured by the Piper Fatigue Scale and in the overall fatigue score. Upon completion of the study, while still blind to the treatment condition, 30 patients indicated that they felt better overall after megestrol, 15 said they felt better after placebo, and 10 indicated no preference (p = 0.001). CONCLUSION: Treatment with megestrol acetate results in rapid and significant improvement of symptoms in terminally ill patients at lower doses than previously reported. The effects are not secondary to nutritional changes. The FLIC quality-of-life questionnaire was unable to detect these changes.

A multicentre phase II study of carboplatin and prolonged oral etoposide in the treatment of cancer of unknown primary site (CUPS).

Cisplatin-based combination chemotherapy is frequently used to treat patients with carcinoma of unknown primary site (CUPS). Response rates in the literature range from 12% to 26% and median survival from 5 to 7 months. The goal of this study was to evaluate the combination of carboplatin and prolonged oral etoposide in patients with CUPS, with the hope of minimizing toxicity but improving efficacy and convenience. Treatment consisted of carboplatin, 300 mg m(-2) on day 1, and oral etoposide 50 mg on days 1-20, every 4 weeks for up to nine cycles. A total of 33 patients were treated and all were evaluable for toxicity. Non-haematological toxicity was mild to moderate, with the exception of one case of grade 4 stomatitis. Grade 4 leucopenia was observed in eight (24%) patients and sepsis in four (12%), with two and possibly three treatment-related deaths. For the 26 patients evaluable for response, the response rate was 23% with responses lasting a median of 11 months (range 7-13 months), with one patient still responding at 12 months. An additional nine patients (35%) had stable disease. Median survival for all patients was 5.6 months (range 2 weeks to 33 months). The combination of carboplatin with prolonged oral etoposide has moderate activity similar to that of other platinum-based regimens and is a well tolerated, convenient, outpatient regimen. Dosing according to estimated creatinine clearance to achieve a carboplatin AUC of 6.0 mg ml(-1) min might have decreased the incidence of severe myelotoxicity without compromising the regimen's efficacy.

Experimental validation of dose distributions predicted by a treatment planning system for complex models.

The trend towards dose escalation in radiation therapy creates the need for non-coplanar beam arrangements to help minimize healthy tissue morbidity in the proximity of treatment volumes. Treatment planning software packages are able to generate external beam non-coplanar isodose distributions and this must be validated before use in a clinical setting. Kodak XV film was used to measure the relative dose within various tissue equivalent phantoms for comparison with the distributions predicted by the G.E. Target ("Target") treatment planning software. The results confirm that Target is able to predict the isodose distribution for coplanar and non-coplanar beams incident on patient equivalent phantoms containing relatively large, semi-infinite inhomogeneities well enough to warrant its implementation into routine clinical use. However, we have found that Target may not be able to adequately predict dose distributions around smaller inhomogeneous inclusions. Further work will be required to investigate this potential problem.

Concurrent use of multiple chemotherapy resistance modulators with etoposide in patients with resistant malignancies.

Since chemotherapy resistance is probably multifactorial, we studied the toxicity and efficacy of adding to etoposide in sequence 5 resistance modulators in the treatment of resistant solid tumors. In cohort 1, metronidazole and ketoconazole were given with i.v. etoposide 100 mg/m(2)/day x 5 days. Because of excessive toxicity, cohort 2 received just metronidazole with etoposide, and metronidazole doses were reduced. Subsequent patient cohorts had the following drugs added to etoposide plus metronidazole: ketoconazole (cohort 3), dipyridamole (cohort 4), tamoxifen [cohort 5 (with etoposide 75 mg/m(2)/day) and 6 (with etoposide 60 mg/m(2)/day)], and cyclosporin (cohort 7). Hence, cohort 7 received daily x 5 i.v. etoposide 60 mg/m(2)/day plus 5 resistance modulators. Forty patients were treated, of whom 38 were evaluable for toxicity. Metronidazole resulted in augmentation of both central neurotoxicity and peripheral neuropathy. Sequential addition of each of dipyridamole, tamoxifen, and cyclosporin appeared to increase hematological toxicity. Some patients also experienced reversible hepatic and renal toxicity. Partial responses were seen in adrenocortical and small cell lung cancers, and minor responses with symptomatic improvement were seen in adrenocortical, small cell lung, non-small cell lung and colorectal carcinomas. Further evaluation of this approach may be warranted in patients with minimal prior chemotherapy exposure.

Etoposide and doxorubicin antagonize the in vitro activity of paclitaxel in human non-small cell lung cancer cell lines.

GOAL: To explore in vitro interactions of paclitaxel with other agents also active against non-small cell lung cancer in the hope of identifying promising combinations for clinical evaluation. METHODS: We measured the cytotoxic effects of paclitaxel when used alone or in combination with vinblastine, cisplatin, etoposide or doxorubicin in final concentrations covering 3-4 Logs in up to five cell lines using a 96-well plate MTT assay. Drug interactions were analyzed with the isobologram method of Steel and Peckham and bidimensional plots. RESULTS: We detected no interactions between paclitaxel and cisplatin in two cell lines. Despite sharing a molecular site of action, there were no interactions between paclitaxel and vinblastine in two cell lines. In contrast, significant antagonism was detected between paclitaxel and etoposide or doxorubicin in 4/5 cell lines tested. CONCLUSIONS: We failed to identify potentially synergistic paclitaxel-based combinations for the treatment of non-small cell lung cancer. Whether the observed in vitro antagonism between paclitaxel and etoposide or doxorubicin predicts for similar interaction in the clinical use of these drugs in combination is unknown.

[Idiopathic scoliosis and the stooping position test]. / La scoliose idiopathique et le test en position penchée vers l'avant.

Idiopathic scoliosis, or scoliosis with no recognizable cause, is the most common form of scoliosis. According to Burrows and Young (1991), the stooped position test (where the child is asked to bend forward) has been used by nurses to test school age children since 1947 and is still the most widely used test for early identification of this condition. To provide an accurate reading of this test, nurses need extensive knowledge of the characteristics of this deformity. They must also be able to note with precision the objective, subjective and evolving signs of idiopathic scoliosis. Statistical information relating to the intrinsic and predictive validity of the test are also important for early detection and referral to a physician. This article describes the symptoms of idiopathic scoliosis, the testing methodology and its validity. The authors also suggest using a scoliometer as a supplementary tool because it measures the degree of spinal deformity and specifies the degree of rotation of the spinal cord.

[The learning needs of the cancer patient: a conceptual analysis]. / Les besoins d'apprentissage de la personne atteinte de cancer: une analyse conceptuelle.

This paper offers a conceptual analysis of the term "learning need" of a cancer population. This analysis was made according to the steps recommended by Wilson (1969). In order to properly understand the essential features of the learning need concept, it is defined by focusing on its characteristics: cognitive knowledge, affective knowledge, psychomotor knowledge and the notion of learning. For the sake of clarity, the expression "learning need" was analyzed by examining a group of closely related concepts: information need, desire to learn and search for information. Although it is often used, the boundary between these concepts is not clearly identified. Some of these concepts may even be confused for each other. The paper concludes by explaining the nature of the cancer patient's learning needs.

[Learning to provide home care]. / Apprendre à soigner à domicile.

More and more social policies are directed at community-based care. As a result, a family member, usually a woman, is called upon to become the caregiver of the sick person at home. In the case of a female caregiver who finds herself providing home care to a recently diagnosed cancer patient, major existential problems must be resolved. Without professional training, this woman must assume major responsibilities for the daily needs of her family member. To maintain a certain degree of control, she must learn to deal with her new situation. Facilitating the learning process becomes an important part of the nurse educator's role. By applying the Knowles theory of adult learning, the nurse educator is better able to understand the learning patterns of adults faced with such problems. This model helps develop a better perception of the adult learner, a clearer vision of the learning involved, and a better understanding of the nurse's role as educator. Before providing information, the nurse takes into account the perceptions of the caregiver and focuses on the person herself--thus recognizing her uniqueness. She helps the learner to become aware of her learning needs, to explore her motivations and to share her experiences. Through her attitude, the nurse communicates her intellectual and emotional availability, and encourages the caregiver to rely on and use her expertise. While providing necessary assistance, the nurse educator is instrumental in allowing the caregiver to take control of her own learning.

In vitro cytotoxicity and differential cellular sensitivity of derivatives of diamino acids. I. N1-methyl, N1-allyl, N1-(2-chloroethyl) and N1-propargyl ureas.

The in vitro cytotoxicity and differential cellular sensitivity of a series of new N1-methyl, N1-allyl, N1-2-chloroethyl and N1-propargyl urea derivatives of diamino acids were determined in the National Cancer Institute's primary antitumor drug screen. The compounds tested showed an in vitro anticancer activity similar to commercialized nitrosoureas such as CCNU, BCNU, MeCCNU, chlorozotocin, streptozotocin and PCNU. The alkylating moiety of the ureas seems to play a role in the general selectivity of our compounds. The N1-methyl and N1-2-chloroethyl urea derivatives are more selective for central nervous system cell lines and the N1-allyl urea derivatives are more selective for lung cancer cell lines. The N1-propargyl ureas did not show any particular selectivity in the 60 human cell lines tested.