orabase and Neutropenia

Phase II studies were conducted to evaluate the safety and efficacy of the interferon inducer Poly ICLC at low doses in advanced renal cancer and relapsed or refractory lymphoma.. Twenty-nine patients with advanced renal carcinoma and eleven patients with lymphoma were treated with poly ICLC. Patients received 0.25 mg/m2 of poly ICLC intravenously twice weekly three days apart until progression or unacceptable toxicity.. There were no objective responses. Six patients with renal carcinoma had stable disease as best response with one patient receiving 62 weeks of therapy. Toxicity included grade 3 anemia in 8 patients and grade 4 anemia in one patient. All patients were anemic prior to entry with a median grade 2 anemia at baseline. Grade 4 neutropenia, thrombocytopenia and injection site pain occurred in one patient each. Grade 3 fever, chills or fatigue occurred in four, three, and three patients respectively. Any grade fever occurred in 10 patients (25.6%) and any grade chills occurred in 9 patients (23.1%).. Poly ICLC at this dose and schedule is well tolerated in both patient populations and is inactive in renal carcinoma.

Topics: Adult; Aged; Carboxymethylcellulose Sodium; Carcinoma, Renal Cell; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Humans; Interferon Inducers; Kidney Neoplasms; Lymphoma; Male; Middle Aged; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Neutropenia; Poly I-C; Polylysine; Thrombocytopenia; Treatment Outcome

Effective treatment of metastatic castration resistant prostate cancer (mCRPC) remains an unmet challenge. Cabazitaxel (CBZ) is approved for mCRPC after docetaxel (DTX) failure, but the improvement in survival is only moderate (∼2 months) and patients suffer from significant side effects. Here, we report the development of a polymer based delivery system for CBZ to improve its safety and efficacy against DTX-resistant mCRPC. CBZ was conjugated to a carboxymethylcellulose-based polymer (Cellax-CBZ), which self-assembled into ∼100 nm particles in saline and exhibited sustained drug release in serum at 10%/day. Cellax-CBZ delivered 157-fold higher CBZ to PC3-RES prostate tumor in mice and could be safely administered at a 25-fold higher dose compared to free CBZ, resulting in superior tumor inhibition in multiple mice models of DTX-resistant CRPC. In a metastatic bone model of CRPC, Cellax-CBZ significantly improves overall survival with a 70% long-term survival rate to day 120, while mice treated with free CBZ had a median survival of 40 days. Cellax-CBZ induced mild and reversible neutropenia in mice but no other tissue damage. Cellax-CBZ showed significant potential for improving therapy of mCRPC over clinically approved CBZ.

Topics: Animals; Antineoplastic Agents; Bone Neoplasms; Carboxymethylcellulose Sodium; Cell Line, Tumor; Delayed-Action Preparations; Docetaxel; Drug Carriers; Drug Compounding; Drug Liberation; Drug Resistance, Neoplasm; Humans; Male; Maximum Tolerated Dose; Mice, Inbred NOD; Mice, SCID; Nanoparticles; Neutropenia; Particle Size; Prostatic Neoplasms, Castration-Resistant; Solubility; Taxoids; Tissue Distribution; Xenograft Model Antitumor Assays

To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients] received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from 1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and amphotericin B orally as well as Orabase and sterilized food, while the patients were nursed in a single room. SD consisted of oral colistin sulphate, neomycin and amphotericin B. Those patients with ANLL were nursed in a single room; patients with ALL were nursed in a single room during remission induction therapy only. All patients except those with ANLL receiving TD received Pneumocystis carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were heterogeneous for diagnosis and chemotherapy the occurrence of fever (central body temperature at least 38.5 degrees C) and major infections (septicaemia of infections of the deep tissues or organs) were registered during periods of neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days). Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had 56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia whereas patients on SD had 11.3. Major infections predominantly consisted of septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD in a non-protective environment does not offer better protection against major infections that SD in patients with ALL or ANLL.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Carboxymethylcellulose Sodium; Cephaloridine; Cephalosporins; Child; Child, Preschool; Colistin; Drug Therapy, Combination; Food Handling; Gram-Negative Bacterial Infections; Humans; Infant; Intestines; Leukemia, Myeloid, Acute; Neomycin; Neutropenia; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sterilization; Trimethoprim, Sulfamethoxazole Drug Combination