Retention studies of recoiling daughter nuclides of 225Ac in polymer vesicles.

Alpha radionuclide therapy is steadily gaining importance and a large number of pre-clinical and clinical studies have been carried out. However, due to the recoil effects the daughter recoil atoms, most of which are alpha emitters as well, receive energies that are much higher than the energies of chemical bonds resulting in decoupling of the radionuclide from common targeting agents. Here, we demonstrate that polymer vesicles (i.e. polymersomes) can retain recoiling daughter nuclei based on an experimental study examining the retention of (221)Fr and (213)Bi when encapsulating (225)Ac.

Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer.

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)-leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m(2)/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m(2), as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU-LV occurred in

A multicenter evaluation of intensified, ambulatory, chronomodulated chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin as initial treatment of patients with metastatic colorectal carcinoma. International Organization for Cancer Chronotherapy.

BACKGROUND: The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated if the drug delivery rate was chronomodulated according to circadian rhythms rather than constant. This allowed the authors to intensify the three-drug chronotherapy regimen and to assess its activity as the initial treatment of metastatic colorectal carcinoma patients in ten centers from four countries. METHODS: Patients with previously untreated and inoperable measurable metastases from colorectal carcinoma received a daily administration of chronomodulated 5-FU (700 mg/m2/day, peak delivery rate at 04:00 hours), LV (300 mg/m2/day, peak delivery rate at 04:00 hours), and 1-OHP (25 mg/m2/day, peak delivery rate at 16:00 hours) for 4 days every 14 days. Intrapatient escalation of 5-FU dose was performed if toxicity was less than World Health Organization (WHO) Grade 2. RESULTS: Of 90 enrolled patients, 35 had a WHO performance status of 1 or 2; 49 had metastases in > or = 2 organs. The liver was involved in 79 patients, 30 of whom had clinical hepatomegaly. The main dose-limiting toxicities were WHO modified Grade 3 or 4 diarrhea (41% of patients, 8.2% of courses), stomatitis (30% of patients, 5.1% of courses), and Grade 2 cumulative peripheral sensory neuropathy (19% of patients after 12 courses). Two patients died with severe gastrointestinal toxicity. Using the intent-to-treat method, the overall objective response rate was 66% (95% confidence limits, 56-76%). Surgical removal of previously inoperable metastases was successful in 31 patients (34%). Histologic necrosis of metastases was >90% in 7 patients and complete in 1 patient. The median progression free survival and survival durations were 8.4 months (range, 5.9-10.9 months) and 18.5 months (range, 13.2-23.8 months), respectively, with 38% of the patients alive at 2 years of follow-up. CONCLUSIONS: The objective response rate appeared to be approximately 3-fold as high as that achieved with current 5-FU-based regimens and translated into an approximately 50% increase in median survival. The hypothesis that this intensified, ambulatory, chronotherapy regimen can increase survival currently is being investigated in a multicenter randomized study conducted by the European Organization for Research and Treatment of Cancer Chronotherapy Study Group.

Long duration of response with vindesine-mitoxantrone-mitomycin (VMMc) combination chemotherapy in metastatic breast cancer: a pilot phase II study.

A total of 39 women with metastatic breast cancer entered a pilot phase II study of the vindesine-mitoxantrone-mitomycin (VMMc) combination chemotherapy. Most of them had received previous chemotherapy [including doxorubicin (27 patients)] for their primary or metastatic disease. The VMMc drugs were given at usual doses. Hematologic side effects were the most serious, leading mainly to leukopenia (five episodes of infection were successfully treated). A 33% partial response rate was obtained (95% confidence limits, 18%-48%), with a median duration (not yet reached) of greater than 510 days (range, 150-720) for the overall population. The median for pretreated patients was greater than 420 days (range, 150-720) which compares favorably with those previously reported in similar patients treated by mitomycin and vindesine or vinblastine.

[Assessment of the quality of life of cancer patients. The preliminary applications to advanced bronchial cancers]. / Evaluation de la qualité de vie chez les malades atteints de cancer. Premières applications aux cancers bronchiques évolués.

So far there is no good evidence that chemotherapy improves survival in non small cell lung cancer. Reports of randomized trials testing chemotherapy versus supportive treatment alone are very few. In recent years, more and more emphasis has been put on the quality of life for cancer patients. Subjective tests such as Anamnestic comparative self Assessment (A.C.S.A. test, Dr. Bernheim) were designed as well as objective ones, using different types of self evaluation. However very few studies have been focused on this aspect in patients with non small cell lung cancer. Therefore the G.E.T.C.B. (Groupe d'Etude et de Traitement des Cancers Bronchiques) decided to initiate a cooperative randomized trial (02 CB 84) in metastatic epidermoid and large cell bronchus carcinoma, in order to test the potential benefit from chemotherapy in these tumors and how it affects the quality of live. In this trial, C.O.P.A.C. combination (Cyclophosphamide, Vincristine, Cis-Platinum, Adriamycin and CCNU) is randomized versus no chemotherapy. The quality of life is assessed monthly on the one hand by a modified A.C.S.A. test performed by a physician and on the other hand by a question list given to the patient. This question list attempts to evaluate the impact of disease as a reference point. Finally protocol 02 CB 84 (activated in 05/84) may give information about the effect of chemotherapy on both survival and quality of life.

[Prevention of chemotherapy-induced alopecia in cancer patients by scalp hypothermia (author's transl)]. / Prévention de l'alopécie des chimiothérapies anticancéreuses par hypothermie du cuir chevelu.

Chemotherapy-induced alopecia observed in cancer patients can now be prevented by a simple, effective, inexpensive and well tolerated procedure: scalp hypothermia. Refrigeration is obtained by placing on the scalp two bags filled with crushed ice 15 minutes before, and removing them 15 minutes after intravenous injection of antineoplastic drugs. Only patients treated with drug combinations that are rapidly administered (into the giving-set tube or by i.v. infusion lasting less than 60 minutes) seem to benefit from scalp hypothermia. The fact that good results were obtained with those drugs (adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate, vincristine) and modes of administration that are most commonly used in women with breast cancer or ovarian cancer makes this procedure extremely interesting.