Comparative efficacy and safety of two fixed ratio combinations in type 2 diabetes mellitus patients previously poorly controlled on different insulin regimens: a multi-centric observational study.

OBJECTIVE: To evaluate the efficacy and safety profile of fixed ratio combinations (FRC) in patients with type 2 diabetes mellitus (DMT2) poorly controlled on different insulin regimens. PATIENTS AND METHODS: This multicentric observational study included 376 patients (157 males, 219 female), with longstanding DMT2 inadequately controlled (HbA1c >7%) on different insulin regimens; premix insulin analogs (MIX) (23.2%), basal-bolus regimen (BB) (30.9%) or basal oral therapy (BOT) (37.1%) to whom FRC was introduced at least 6 months prior to data collection. RESULTS: Median age of patients was 67 years, with the duration of diabetes for 14 years, median HbA1c of 8.4% and BMI of 34.35 kg/m2. The proportion of patients treated with IDegLira and IGlarLixi was similar (48.4% vs. 51.6%). There was a borderline difference regarding regimen groups (p = 0.059) implying the greatest improvement of HbA1c in the MIX group. The significant interaction between BOT and BB/MIX regimens (p = 0.011) was noted indicating the largest reduction of BMI in BB and MIX groups. After the FRC administration, there was no significant difference in gastrointestinal (GIT) side-effects. The number of patients with hypoglycemic episodes decreased from 24% to 7% after FRC initiation (p < .001). The group using IGlarLixi required a significantly higher average dose steps compared to IDegLira (p < .001 for all) to achieve glycemic goals, while a larger proportion of patients using IDegLira lost more than 5 kg, compared to IGlarLixi (p < .001). Significant improvement was observed in all glycemic parameters in all insulin treated patients after replacement of insulin therapy with FRC (p < .001 for all). Composite outcome defined as any weight loss and HbA1c below 7% was accomplished in 20.3% of patients. CONCLUSIONS: In real life setting switching to both FRC options in people with longstanding inadequately controlled DMT2 treated with different insulin regimens could offer an effective therapeutic choice for achieving glycemic goals, with an improved safety profile.

Bi-weekly vincristine, epirubicin and methylprednisolone in alkylator-refractory multiple myeloma.

Nine patients with poor-prognosis, alkylator-refractory stage III multiple myeloma (MM) were treated with a 23-h continuous infusion (CI) of a compatible mixture of vincristine (VCR) and epirubicin (EPI) daily for 4 days along with a daily 1-h infusion of high-dose methyl prednisolone (MP) to total of 5 days (VEMP); cycles were repeated every 2 weeks when possible, usually on an outpatient basis. WHO grade 3 or 4 neutropenia and infection were the predominant toxicities encountered, necessitating some treatment delays and dose reductions. Two patients died during treatment. Peripheral neuropathy necessitated discontinuation of the VCR in six patients without obvious loss of efficacy of the regimen. Skeletal muscle dysfunction and cardiomyopathy did not occur; trivial ECG abnormalities occurred during a minority of infusions but were of indeterminate relationship to the chemotherapy. Confusion occurred in two patients; alopecia was frequent but reversible, and mild/moderate dyspepsia and stomatitis were common but easily managed. Eight patients achieved a partial response (PR); another patient experienced early death during his second cycle before response assessment. The median survival from the first VEMP administration was 9 months (range, 1-64 + months), the median response duration was 7 months (range, 1-64 + months). Two patients experienced responses too short to be clinically relevant (< or = 2 months). An analysis of weekly paraprotein estimations suggests that the intended bi-weekly cycle length may be optimal. Six of these nine patients derived major benefit from this bi-weekly regimen, which deserves further exploration.

High-dose etoposide in the treatment of relapsed primary brain tumors.

Twenty-four patients with relapsed primary intracranial tumors were treated with high-dose etoposide (600-1000 mg/m2). All patients had received previous radiotherapy and 15 had had previous chemotherapy. The treatment was well-tolerated, with little toxicity. Only one patient showed a partial response, which was maintained for 78 weeks. Four patients had stable disease, for a median of 15 weeks. Etoposide failed to show useful activity in relapsed brain tumors.

Assay of anti-cancer drugs in tissue culture: relationship of relapse free interval (RFI) and in vitro chemosensitivity in patients with malignant cerebral glioma.

One hundred and seventeen patients with cerebral glioma (Kernohan grades III and IV) were treated with adjuvant chemotherapy using procarbazine (PCB), CCNU and vincristine (VCR) following whole head irradiation. Cell cultures were prepared from 40 patients in this series and their sensitivity to each cytotoxic drug was assessed in a mictotitration assay with 35 S-methionine incorporation as the end point. Twenty-two of forty (55%) patients responded to PCB and/or CCNU in vitro, and sensitivity to these drugs was linked with increased RFI, whilst sensitivity to VCR was not. The RFI of patients who had responded to PCB or CCNU in vitro was significantly longer than the RFI of patients whose tumours failed to respond in vitro or patients who had not been tested. There was no difference in sex ratio, extent of operation, radiation dose and degree of steroid cover between responders, non-responders and untested groups. Grade III tumours tended to be more sensitive in vitro than grade IV tumours. The age of patients also influenced in vitro chemosensitivity. Patients with chemosensitive tumours in vitro tended to be younger than patients with insensitive tumours in vitro. Further statistical analysis, taking into account these prognostic factors, indicated an association between chemosensitivity in vitro and RFI.

Low-dose aminoglutethimide in treatment of advanced breast cancer.

The clinical and endocrine effects of low-dose aminoglutethimide without hydrocortisone in patients with advanced breast cancer were investigated. In a dose escalation study low-dose aminoglutethimide alone (62.5-125 mg twice daily) was as effective as conventional doses with hydrocortisone in lowering serum oestrone and oestradiol concentrations but caused minimum adrenal inhibition, as assessed by serum dehydroepiandrosterone sulphate. 11 of 57 (19%) evaluable patients had tumour regression by objective criteria on this treatment, but the frequency of side-effects was similar to that with conventional doses. Low-dose aminoglutethimide is active in the treatment of breast cancer. It appears to work by inhibition of the aromatase enzyme system in peripheral tissues rather than adrenal suppression.

Mitoxantrone: an active new agent in the treatment of advanced breast cancer.

Sixty-five patients with advanced breast carcinoma were treated with mitoxantrone, an anthracenedione with structural similarities to adriamycin. The series included 26 patients who had received no prior chemotherapy. Treatment was given in a dose of 12-14 mg/m2 by IV infusion, repeated every 3 weeks. Sixty-two patients were evaluable for response, but all were evaluable for toxicity. One (2%) achieved a complete response and 18 (29%) a partial response (overall response rate 31%). The response rate in patients who had received no prior chemotherapy was 35%, vs 22% in previously treated patients. The median duration of response was 10 months (range 3.5-18.5 months). Two responders had previously failed to respond to adriamycin, and a third responder subsequently failed to respond to adriamycin. Neutropenia was the most frequently seen toxicity, with a WBC of less than 2,000/mm3 seen in 26 patients (40%), eight of whom (12%) had a neutropenic infection. Thrombocytopenia (less than 100,000/mm3) occurred in 12 patients (18%), but in three of these only after at least 6 months of treatment. Two patients developed readily reversible cardiac failure after prolonged treatment (11-13 months). Other toxicities were in general mild, and the drug was well tolerated: severe alopecia occurred in only one patient. Mitoxantrone is an active well-tolerated agent in the treatment of advanced breast carcinoma, but the risk of neutropenia requires careful supervision. The long-term risk of cardiotoxicity cannot yet be fully assessed.

Mitoxantrone (Novantrone) as single agent and in combination chemotherapy in the treatment of advanced breast cancer.

Nineteen out of 62 evaluable patients with advanced breast cancer achieved an objective tumour response to mitoxantrone (31%) given in a dose of 12-14 mg/m2 by i.v. infusion repeated at 3-weekly intervals. The response rate in patients who had received no prior chemotherapy for advanced disease was 35%, compared with 22% in previously treated patients. Median duration of response was 10 months. Responses were seen in three out of nine patients who failed to respond to adriamycin. Neutropenia was dose limiting and eight out of 65 patients evaluable for toxicity had a neutropenic infection. Two patients developed readily reversible cardiac failure and two more developed physiological features of cardiac impairment, all after prolonged treatment. Other toxicities were mild and the drug was well tolerated; severe alopecia occurred in only one patient. Nine patients treated with a combination of mitoxantrone, vincristine and methotrexate all developed leukopenia with a mean white blood count of 1400/mm2 (range 200-2400) although no episodes of neutropenic infection were seen and the combination was otherwise well tolerated. Mitoxantrone is an active, well tolerated drug in the treatment of advanced breast cancer and merits further evaluation.