Current status of clinical indications for hematopoietic growth factors after chemo-/radiotherapy in gynecology

With the identification and recombinant production of the hematopoietic growth factors, these cytokines have been evaluated in the treatment of primary bone marrow failure states and following myelosuppressive chemotherapy or radiotherapy. An increasing number of clinical trials with hematopoietic factors have been performed in patients with haematological and oncological diseases. Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin and, in phase I/II trials, thrombopoietin (TPO) are available for the clinical use. Most studies have been performed with G-CSF and GM-CSF, their beneficial effects are proven regarding acceleration of hematopoietic recovery following chemotherapy. This results in a marked reduction of infectious risks and a shortening of drug- and radiation-induced myelosuppression. CSFs are most important in mobilizing peripheral blood progenitor cells (PBPC) and have allowed high-dose therapy combined with stem cell support in gynecological malignancies, e.g. ovarian carcinoma and breast cancer. However, evidence based, clinical practical guidelines for the use of hematopoietic growth factors in gynecological malignancies are not for all circumstances available.     

Ceftriaxone in the outpatient treatment of cancer patients with fever and neutropenia

A study was performed in low-risk cancer patients with chemotherapy-induced febrile neutropenia to determine the safety and efficacy of ceftriaxone given in an outpatient setting. A total of 126 episodes of febrile neutropenia in 120 clinically stable outpatients were treated with intravenous ceftriaxone alone (n=100) or in combination with other antibiotics (n=26). The mean neutrophil count was 460/mm3; severe neutropenia (< 100/mm3) was observed in 18 episodes. The initial treatment with ceftriaxone (alone or in combination) was successful in 99 episodes (78%). Ninety-five episodes (76%) were successfully treated in an outpatient setting only; admission to hospital was necessary in 31 episodes (24%), but no infection-related death was observed. Ceftriaxone seems to be safe and effective for outpatient therapy of patients with low-risk febrile neutropenia.     

Thermally Stable and Solvent Resistant Mesoporous Honeycomb Films from a Crosslinkable Polymer

The preparation of mesoporous honeycomb films, also known as breath figure arrays (BFAs), from poly(styrene‐co‐maleic anhydride) is reported. Films containing regular arrays of micrometer‐sized air‐holes were prepared by evaporation of a chloroform solution of a mixture of the above polymer including 10 % of an amphiphilic polyion complex under high humidity that leads to the formation of a hexagonally packed monolayer of water droplets in the polymer film. The porous films were characterized by optical and scanning electron microscopy. Crosslinking was achieved by immersion in an ethanol solution of an α, ω alkyldiamine and the chemical reaction was monitored by infrared spectroscopy. The non‐crosslinked films are hydrophobic with a water contact angle of more than 90°, whereas the crosslinked films became hydrophilic, so that a water drop penetrated into the films. After crosslinking, the honeycomb structure was stable to up to 350 °C, an increase of more than 150 K as compared to the non‐crosslinked films.     

Mesoscopic 2-D ordering of inorganic/organic hybrid materials

Organic–inorganic hybrid materials with micronsized (i.e., mesoscopic) network structures are expected to have interesting properties and applications in various fields, such as separation, catalysis, biomineralization, or quantum optics. Here a new method is introduced to produce thin films of two-dimensionally ordered honeycomb structures. Casting a chloroform solution of a mixture of organic amphiphiles with metal acetylacetonates or -alkoxides at high atmospheric humidity leads to the formation of a closely packed layer of water droplets on top of the organic solvent. The water acts as a template, After evaporation of the chloroform and the water, a honeycomb structure remains. Pyrolysis of the metal alkoxides films lead to the formation of microporous metal oxide (e.g., anatase, one of the catalytic active titanium oxides).     

Possibilities and limits of ambulatory supportive measures in oncology exemplified by antibiotic therapy of febrile neutropenia

Neutropenia is common after intensive chemotherapy. Hospitalization and intravenous broad-spectrum antibiotics are the standard of care for febrile neutropenic patients because of the risk of serious complications and associated mortality. Short neutropenic periods (< 7 days) are considered to be at a low-risk in cases when fever occurs in clinically stable patients. Recent work suggests that such a low-risk population of febrile neutropenic patients might benefit from alternatives to inpatient care. The agents that best qualify for outpatient treatment include quinolones i.v./p.o., glycopeptides, ceftriaxone and aminoglycosides, particularly if the latter are given once daily. Response rates to antimicrobial therapy range from 80 to 95% in low-risk febrile neutropenia episodes. Treating these patients in an outpatient setting avoids hospitalization in 75 to 95%. There is no doubt that outpatient therapy may have several advantages, including lower costs and an improved quality of live. Outpatient antibiotic therapy for febrile low-risk neutropenia should be considered as an acceptable alternative to inpatient treatment.     

Effect of topical oral G-CSF on oral mucositis: a randomised placebo-controlled trial

Oral mucositis is a dose-limiting toxicity of intensive chemotherapy. It is caused directly by the cytotoxic effect of chemotherapeutic agents and indirectly by sustained neutropenia. Severe oral mucositis is an important predisposing factor for life-threatening septic complications during aplasia. It also reduces quality of life. At present, no effective causal prophylaxis or treatment against oral mucositis is established. We performed a prospective randomised placebo-controlled trial using topical oral r-metHuG-CSF (filgrastim) in high-grade lymphoma patients treated according to the B-NHL protocol, which contains high-dose methotrexate and causes severe oral mucositis (WHO grades I-IV) in >50% of patients. Between August 1996 and July 1997, a total of 32 chemotherapy cycles were documented in eight patients (four male, four female). Mucosal erythema and ulceration were recorded. All patients assessed their oral pain and impact on swallowing daily, using a subjective scale from no to maximal discomfort (1-10). In addition, oral mucositis was assessed according to the WHO score. Filgrastim was administered in 16 cycles as a viscous mouthrinse (carboxymethylcellulose 2%, oleum citrii) 4 x 120 microg/day from days 10 to 16. Sixteen cycles were given to control patients, of these 14 with placebo, and another two cycles with no treatment. Severe mucositis (WHO grade III/IV) was documented in 21 of 32 cycles (65.5%). A difference of borderline significance was observed for the reduction of maximum severity of oral mucositis between G-CSF vs placebo (P = 0.058), with a reduction of WHO grade IV of 50% (four G-CSF vs eight control). The number of days in hospital was reduced significantly in the G-CSF group (P = 0.02). In conclusion, topical oral G-CSF mouthrinses may be beneficial to reduce oral mucositis.