Phase I Trial of Methotrexate-Albumin in a Weekly Intravenous Bolus Regimen in Cancer Patients

There is growing interest in measuring quality of life (QoL) in medicine. Together with objective variables such as healing rate, as recorded with endoscopy, this is believed to give a better basis for evaluation of treatment regimens in patients with upper gastrointestinal diseases.

The neurological symptoms caused by tumor compression of the spinal chord disappeared. After another two injections, slight stomatitis (grade 2) reappeared. MTX-HSA treatment was continued, but intervals were prolonged to injections every second or third week.

A strategy for the assessment of QoL in patients with upper gastrointestinal symptoms is presented here. The QoL evaluation was based on a battery of questionnaires, covering both general and specific aspects of life. General well-being was evaluated with the Psychological General Well-being Index (PGWB), and subjective symptoms with two specific questionnaires, the Gastrointestinal Symptom Rating Scale (GSRS) and the Ulcus Esophagitis Subjective Symptoms Scale (UESS). This new strategy was applied clinically in a study including 146 outpatients with suspected peptic ulcer. Initially, the patients reported a low degree of general well-being as evaluated with the PGWB, but the values returned to those found in normal populations within 4 weeks.

MRI was available in five controls. While MRI was normal, FOI showed minimal changes in CI and P2 (1 out of 60 joints, 1.2%, and 2 out of 60 joints, 3.3%) and none in P1 and P3. CE and laboratory tests (erythrocyte sedimentation rate (ESR) and C reactive protein (CRP)) were performed. Clinical swollen and tender joints (including distal interphalangeal joint (DIP)) were scored for presence and absence (0-1). The Disease Activity Score 28 (DAS28)18 was used to assess disease activity in patients with RA, psoriatic arthritis (PsA) and undifferentiated arthritis (uA).

The evaluation of the success of therapy for gastroesophageal reflux disease (GERD) has thus far been primarily on the basis of the endoscopic evaluation of the ability of drugs to heal esophageal mucosal breaks and to a lesser extent on their ability to decrease the diverse symptoms of acid reflux. However, because most patients with GERD have no visible esophageal lesions using conventional endoscopic methods, this paradigm requires serious reconsideration. As patients with nonerosive reflux disease (NERD) are just as symptomatic as patients with erosions and are no easier to treat the use of endoscopic end points alone, as criteria for determining healing and efficacy of therapy requires reassessment. In addition, the symptoms of GERD are now appreciated to be broad-based, including many extraesophageal symptoms that contribute to the marked reduction in quality of life for GERD patients. For this reason, and because endoscopic criteria cannot be applied to evaluating therapy in NERD, the success of GERD therapy should be judged primarily in terms of diminishment of GERD-related symptoms–a return to the traditional way that patients judge therapeutic success.

This observation supports the interpretation that the disagreement of FOI with MRI and US in the majority of cases did not result from false-positive findings. ICG-enhanced FOI with the Xiralite system is a new imaging technology. To our knowledge, this is the first study to evaluate the application in patients with arthritis and to compare it with CE, US and MRI.

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  • Grade 2 stomatitis was observed, and the treatment was paused.
  • Correlations between HRQOL and FSSG were investigated and logistic regression analysis was performed.
  • Disagreement of FOI and MRI mainly resulted from the higher rate of positive findings in FOI.
  • FOI findings were compared with clinical findings in 750 joints (128 tender, 148 swollen, 83 swollen and tender).

Allergic reactions or other acute toxic reactions did not occur, even in patients with tumor responses, each patient receiving more than 35 injections of MTX-HSA. This study evaluated changes in health-related quality of life (HRQL) outcomes of once-daily omeprazole compared with ranitidine for the short-term treatment of patients with poorly responsive symptomatic gastroesophageal reflux disease (GERD).

Evaluation of the GSRS and UESS with regard to internal consistency, construct validity, and the ability to detect changes showed them to be satisfactory. The psychometric documentation of the measures indicates that they may give reliable and clinically valid information when used for evaluation of medical treatments in upper gastrointestinal disease. Further documentation of the methods is, however, needed to establish a generally acceptable QoL assessment in gastroenterology. Many questionnaires that assess subjective symptoms or health-related quality of life (HRQOL) have been developed to confirm the efficacy of treatment in patients with gastroesophageal reflux disease (GERD). However, few reports have correlated early improvements in scale scores with predictions of subsequent therapeutic responses.

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Therapeutic Activity of MTX-HSA

In experimental models of arthritis, FOI findings corresponded to histologically proven synovitis. This is the first comparative study of FOI with other imaging modalities in humans with arthritis.

After the Phase I study period of 8 weeks, treatment intervals could be prolonged in responding patients. DLT was defined according to CTC. Critical parameters were grade 3 toxicity for hematological parameters; coagulation parameters; stomatitis; diarrhea; gastritis; gastrointestinal tract ulcers; mucositis; diseases of the lung, kidneys, urinary tract, skin, eyes, and ears; and neurological or autoimmune disorders. CTC grade 4 toxicity was chosen for hepatic function, metabolic disorders, vascular diseases, loss of appetite, and alopecia. Toxicity for each patient was assessed every week.

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