Inflammatory markers predict insulin sensitivity in active rheumatoid arthritis but not in psoriatic arthritis.

Whether the insulin resistance commonly observed in patients with inflammatory arthritis is a disease-specific feature and/or is limited to a disease phase (i.e., it occurs only during phases of high disease activity) is unknown. Fifty-three rheumatoid arthritis (RA) and 44 psoriatic arthritis (PsA) patients were recruited consecutively along with 194 controls matched for age, sex and body mass index for a case-control study. All underwent an oral glucose tolerance test, the results of which were analysed to derive the following indexes: homeostatic model of insulin resistance (HOMA-IR), insulin sensitivity index (ISI) and early insulin sensitivity index (EISI). These data were related to anthropometric, clinical and laboratory findings. Metabolic parameters of patients and controls were similar. Neither inflammatory markers nor disease activity scores were related to glucose metabolism for the generality of RA and PsA patients; however, by restricting the analysis to the subset of RA patients with residual disease activity, an association emerged between erythrocyte sedimentation rate, on the one hand, and fasting insulin (ß=0.46, p=0.047) and HOMA-IR (ß=0.44, p=0.02), on the other. Moreover, C-reactive protein (CRP) levels were associated with plasma glucose and insulin levels measured 120 min after the glucose load (ß=0.91, p=0.0003 and ß=0.77, p=0.0006, respectively); ISI and EISI were predicted by CRP (ß=-0.79, p=0.0006; ß=-0.80, p=0.0001, respectively). The same did not hold true for PsA patients. The association between systemic inflammation and insulin resistance indexes is a feature of RA with residual disease activity, not a universal feature of inflammatory arthritides.

Phase I study of escalating dose mitoxantrone in combination with alpha-2-interferon in patients with advanced solid tumors.

In vitro and preclinical in vivo data have shown a synergistic antitumor activity between alpha-interferon and some antiproliferative agents. A phase I study of the concurrent administration of interferon-alpha 2 and mitoxantrone was initiated, to determine the maximum tolerated dose of mitoxantrone given i.v. every 3 weeks in escalating doses combined with a fixed dose of s.c. interferon alpha 2 (6 x 10(6) IU three times per week 3), in patients with advanced solid tumors resistant to conventional chemotherapy. At least three evaluable patients were entered in each dose level of mitoxantrone starting at 4 mg/m2, with no escalations allowed in the same patient. Twenty-seven patients received a total of 101 cycles and five dose-levels were explored (4-6-8-10-12 mg/m2 of mitoxantrone). The dose-limiting toxicities were leukopenia and granulocytopenia at 12 mg/m2 of mitoxantrone, at which dose hematological toxicity occurred in greater than 50% of cases, with one patient presenting grade 4 leuko-granulocytopenia. No severe thrombocytopenia occurred. In the majority of patients transient hepatic enzyme elevations and a flu-like syndrome due to interferon alpha 2 were observed in all dose-levels explored. These observations suggest that the hepatotoxic effects of interferon alpha 2 do not emphasize mitoxantrone side-effects if given simultaneously. When mitoxantrone is administered with 6 x 10(6) IU of interferon alpha 2, the recommended dose for future phase II studies is 10 mg/m2/weeks 3 with escalation up to 12 mg/m2 in selected patients if such a combination is well tolerated in terms of myelosuppression. Regarding therapeutic activity, four out of 25 (16%) cases evaluable for response achieved a partial response.(ABSTRACT TRUNCATED AT 250 WORDS)

Weekly epirubicin versus doxorubicin as second line therapy in advanced breast cancer. A randomized clinical trial.

Forty-nine patients with advanced breast cancer who had failed from first-line cyclophosphamide, methotrexate, and 5-fluorouracil (CMF regimen) chemotherapy, were randomized to treatment with either epirubicin (Epi) or doxorubicin (Dox) at a dose of 20 mg/m2 given intravenously (i.v.) weekly to compare the efficacy and toxicity of these two anthracyclines given in such a schedule. Of 43 evaluable patients 36% (eight of 22) treated with Epi and 38% (eight of 21) treated with Dox achieved a complete plus partial response rate (95% confidence limits 16-56% +/- 20% and 18-58% +/- 20%, respectively). Patients who obtained a major therapeutic response to previous CMF exhibited a significantly higher response rate with both the drugs: seven of eight (87.5%) compared with one of 13 (8%); p less than 0.05 for Epi and six of seven (86%) compared with two of 15 (13%); p less than 0.05 for Dox. The median duration of response was 4.5 months with Epi compared with 7 months with Dox, and the median survival of the two groups of patients were superimposable (12 months with Epi versus 11 months with Dox). The median cumulative dose was 220 mg/m2 (range 160-620) and 240 mg/m2 (range 160-860) for Epi and Dox, respectively. Gastrointestinal and hematological toxicities were moderate for both the drugs, with fewer episodes of nausea and vomiting, stomatitis, and leukopenia following Epi administration. A very low incidence of alopecia was recorded for both the drugs. Regarding cardiac evaluation, no significant differences were evident; however, the only case that developed symptomatic congestive heart failure was in the Dox arm, after a cumulative dose of 820 mg/m2 at 11.5 months. Epi given weekly at low doses preserves efficacy in the treatment of patients with advanced breast cancer, and given at equimolar doses, has a slightly better therapeutic index than the parent compound.

Characterization of node-negative breast cancer by clinico-pathologic and biologic factors.

About 30% of node-negative breast cancer (NNBC) patients relapse and about 20-25% die after local treatment. This is a heterogenous disease and at present no single factor completely distinguishes those patients destined to have a recurrence and to die, for whom an adjuvant treatment seems indicated. With the objective of subdividing NNBC into different prognostic groups, we studied the expression and relationship of eight factors related both to the clinico-pathologic characteristics and to the tumor biology in 78 consecutive patients: menopausal status, tumor size, grading (G), intratumoral vascular invasion (IVI) steroid hormonal receptors, proliferative rate and epidermal growth factor receptor (EGFr) expression. The frequencies of the risk factors examined were: pre- or perimenopausal status in 29.5%, tumor size greater than 2 cm (pT2) in 28%, GIII in 45%, IVI in 13% estrogen receptor (ER)-negative in 43% and progesterone receptor (PgR)-negative in 60%. There were 23% high proliferating (Ki-67 antibody greater than 20%) and 54% EGFr positive tumors. The distribution of the above risk factors in each tumor were: no factor in 4%; one in 15%; two in 30%; three in 23%; four in 14%; five in 8%; six in 2%; seven in 4% and no case had the sum of all the factors. The mean distribution value was of two per case. Twenty-eight percent of patients had more than the sum of four factors. A significant correlation was observed among: premenopausal status with G III (61% vs 45% in postmenopausal status; p less than 0.05), premenopausal status with ER-negative tumors (65 vs 29% in postmenopasual; p less than 0.05) and between the lack of expression of the two hormonal receptors (overall agreement of 77; p less than 0.05). The prognostic value of these findings needs to be verified with an adequate follow-up.

[Advanced stages of rectosigmoid cancer. The role of postoperative radiotherapy]. / Stadi avanzati del cancro del sigma-retto. Ruolo della radioterapia postoperatoria.

In patients with advanced rectosigmoid adenocarcinoma treated with radical surgery alone, loco-regional relapse rate is quite high (29%-60%). When postoperative radiotherapy is performed, loco-regional relapse rate sharply falls to 7%-15%. A series of 42 patients, stage B2, C1 and C2, is presented. All patients were treated with radical surgery and postoperative radiotherapy. Only two loco-regional relapses were found (5%). Overall actuarial survival at 5 years is 76% for B2, and 46% for C1 and C2. The authors conclude that adjuvant postoperative radiotherapy is useful in reducing loco-regional relapses, whereas survival seems to be improved only for stage B2 patients.

[Small size breast cancer conservative surgical therapy and subsequent radiotherapy]. / Il cancro mammario di piccole dimensioni: terapia chirurgica conservativa e successiva radioterapia.

From february 1980 to december 1985, 115 breast carcinomas were treated with QU.A.RT. with limited surgery and following radiotherapy. Median age was 51 years (range 25 to 75). Surgical approach was quadrantectomy with axillary nodes dissection. Irradiation of residual breast was performed by an anterior high energy electron beam. 50 Gy in 25 fractions was the minimal dose to whole breast. In pN+ patients systemic adjuvant therapy was done. Local control was obtained in 111 cases. Local recurrence appeared in 4: 1 menopausal pT1 pNO and 3 premenopausal (1 pT1 pNO and 2 pT1 pN+) at respectively 31, 19, 22 months from diagnosis. Distant metastases appeared in 10 patients. 7 died for cancer and 3 are still alive. Cosmetic results were scored as good in 52, better than mastectomy in 26, unsatisfactory in 3, and not stated in 34. Our results are comparable to those of other Centers. Youth, axillary metastases and delay between surgery and radiotherapy appears to influence the risk of recurrence also in our series.