Aristidis Polyzos

A comparative study of intraperitoneal carboplatin versus intravenous carboplatin with intravenous cyclophosphamide in both arms as initial chemotherapy for stage III ovarian cancer.

Cisplatin (C) or carboplatin (CBP) plus cyclophosphamide (CTX) was until recently considered standard chemotherapy for advanced ovarian cancer (OC). Attempts to maximize platinum and its analog activity against OC include its administration directly into the peritoneal cavity. In the past we have shown that intraperitoneal (IP) CBP administration is a safe and effective treatment for OC [Polyzos et al: Proc Am Assoc Cancer Res 1990;31: 1120]. In the present study we aimed to compare the effectiveness and toxicity of CBP administration either intravenously (IV) or IP plus CTX IV. Since 1990, 90 evaluable patients with stage III OC were prospectively randomized to receive CBP 350 mg/m2 IV or IP plus CTX 600 mg/m2 IV (in both groups) every 3–4 weeks for six courses. The randomization incorporated stratification according to performance status and the amount of residual tumor (maximum diameter ≤2 or >2 cm). Clinical assessment was performed with abdominal CT and serum CA-125. Responses were observed in 33/46 = 72% (95/CI 56.5–84.0) of the IV group and in 33/44 = 75% (95/CI 59.7–86.8) of the IP group with 48 and 45% clinical complete responses, respectively. Times to progression were 19 months (8–62+) for the IV group and 18 (6–72+) for the IP group. Median survivals were: 25 months (6–80+) and 26 months (6–72+), respectively. Significantly more patients in the IV group than in the IP group had grade 3 or higher leukopenia (p < 0.01) and grade 3 thrombocytopenia (p < 0.09). Morbidity due to infectious complications in the IP group was minimal. It seems that IP CBP is equally effective to IV administration in terms of response and survival with less myelotoxicity. The favorable results on survival demonstrated in studies with IP C administration in patients with small volume disease [Alberts et al: N Engl J Med 1996;335:1950–1965] could not be repeated in the present study applying CBP in patients with variable tumor size and a relatively small number of patients. The likelihood that patients with large volume disease would benefit from a regional approach compared to systemic administration is small and this explains the inability to detect a difference between the two arms.

Circulating adiponectin levels and expression of adiponectin receptors in relation to lung cancer : two case-control studies

Background: Decreased circulating levels of adiponectin, an adipocyte-secreted hormone and endogenous insulin sensitizer, have been associated with several obesity-related malignancies. Thiazolidinedione administration, which increases adiponectin levels, decreases risk for lung cancer. Whether circulating adiponectin levels are associated with lung cancer and/or whether adiponectin receptors are expressed in lung cancer remains unknown. Methods: We conducted a case-control study of 85 patients with incidental, histologically confirmed lung cancer and 170 healthy controls matched by gender and age. In a separate study, archival lung specimens from 134 cancerous and 8 noncancerous tissues were examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry. Results: Tobacco smoking, heavy alcohol intake and education were all associated with lung cancer risk, whereas serum adiponectin levels were not significantly different between cases and controls (multiple logistic regression, odds ratio per SD of adiponectin among controls: 1.13, 95% confidence interval: 0.64–2.02). Adiponectin levels were significantly lower (odds ratio: 0.25, 95% confidence interval: 0.10–0.78) among patients with advanced compared to those with limited disease stage. Expression of adiponectin receptors was apparent only in the cancerous lung tissue (64.2% AdipoR1 and 61.9% AdipoR2 in cancerous vs. 0% among noncancerous tissue). Specifically, AdipoR1 was expressed in all disease types, but no difference was noted with disease stage, whereas AdipoR2 was mainly expressed in the non-small cell carcinomas and more prominently in the advanced disease stage (80%). Conclusions: Circulating adiponectin levels are not different in cases of this malignancy – which seems to be unrelated to obesity and insulin resistance – compared to their healthy controls, though hormonal levels were significantly lower in advanced versus limited lung cancer. Both adiponectin receptors were expressed in cancerous lung tissue, but not in normal control tissue and there was a differential expression by disease stage. These findings should be further explored, especially in the context of the recently reported protective effect of thiazolidinediones in diabetic patients with lung cancer.

Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma and various other solid tumors.

SU11248 sunitinib malate sutent is a selective inhibitor of certain protein tyrosine kinases including VEGF-R types 1-3 PDGF-R-a and -b, c-kit, and RET. Its antitumor activity may result from both inhibition of angiogenesis and direct antiproliferative effects on certain tumor types. In several phase I/II/III studies, sutent was found to be effective as second and first line treatment in metastatic renal cell carcinoma (RCC). In fact, with a 37% response rate and an additional 48% stable disease sutent became the drug of choice for first line treatment in RCC. Sutent was also effective as second line treatment in patients with gastrointestinal stromal tumors (GIST) with 8% response rate, 70% stable disease and a 20-month median survival. Prolonged stable disease was also documented in neuroendocrine tumors. In addition, a phase II study in multitreated women with breast cancer, sutent demonstrated a moderate activity with 16% clinical benefit. Finally, in non-small cell lung cancer (NSCLC) in patients progressing on chemotherapy sutent was able to achieve a 10% response rate, a level of activity similar to those documented by other agents approved for lung cancer. The agent is being tested in other tumors with a modified schedule of dosage.

Role of malignancy and preoperative embolization in the management of carotid body tumors.

The purpose of this retrospective study is to present our approach to the management of patients with carotid body tumors (CBTs), emphasizing the role of malignancy and preoperative embolization. Between 1975 and 1998 a series of 18 patients with CBTs were treated, and 16 of them underwent successful excision of the tumor. According to the Shamblin classification, six of the tumors were type I, six type II, and six type III. In three of these patients (two with type II tumors and one with type III) in whom preoperative embolization had been performed, mean intraoperative blood loss was 400 ml, whereas in the remaining 13 cases this loss was 700 ml. Two patients with intracranial tumor spread underwent only radiotherapy. Neither postoperative deaths nor strokes occurred. Temporary cranial nerve injury occurred in four cases (25%). Local lymph node invasion was found in two patients, establishing the diagnosis of malignancy. One of these patients developed distal metastases 3 years after the operation and was treated with radiotherapy and octreotide. Follow-up ranging from 30 months to 23 years (mean 5 years) revealed no local recurrence except for the two patients who were treated with radiotherapy only. In conclusion, surgical excision remains the treatment of choice for CBTs and can be performed without major risks and with low morbidity and mortality. Preoperative embolization is helpful by diminishing intraoperative bleeding, and malignancy, though rare justifies early management.

Gemcitabine and docetaxel as second-line chemotherapy for patients with nonsmall cell lung carcinoma who fail prior paclitaxel plus platinum-based regimens.

Treatment options for patients with recurrent nonsmall cell lung carcinoma (NSCLC) remain limited as a result of poor activity of older agents after platinum‐based therapy. In the current Phase II study, the authors evaluated the combination of gemcitabine and docetaxel in patients with recurrent NSCLC.

Elevated Serum Leptin Levels: A Risk Factor for Non-Small-Cell Lung Cancer?

Objective: Leptin is intimately intertwined in the molecular pathophysiology of several cancer types; with regard to lung cancer, however, limited research has been conducted, with overall conflicting results. Methods: The present case-control study comprises 66 non-small-cell lung cancer (NSCLC) cases and 132 healthy controls matched for gender and age. Lifestyle, sociodemographic and medical history information has been obtained in addition to body mass index (BMI) measurements and weight change during the last 2 months. Serum leptin and adiponectin levels were determined following a standard protocol. Results: In multiple logistic regression analyses, elevated serum leptin emerged as a risk factor for NSCLC independent of central obesity, more pronounced after controlling for BMI and recent weight loss (odds ratio = 4.58, 95% confidence interval: 1.94–10.82). Additionally, smoking and animal foods consumption were strongly associated with the disease, whereas plant foods consumption showed a protective association. Conclusions: The observed higher serum leptin levels in NSCLC cases might be attributed to direct or indirect effects mediated by cancer- or cachexia-related cytokines. In line with the growth-promoting properties of leptin in the lung tissue documented elsewhere, increased serum leptin concentration may represent a tumor-promoting event during non-small-cell lung carcinogenesis.

The smoking‐cessation promotion practices of physician smokers in Greece

In order to investigate Greek physicians smoking habits and how these affect their role in promoting smoking cessation, a survey of 148 hospital physicians was undertaken. According to their answers, 44% of the internists and 54% of the surgeons admitted to smoking more than 20 cigarettes per day for at least five years. Major obstacles for quitting were their personalities (70-80%) and stress in hospitals (40%). For those willing to quit, an antismoking policy in their homes (32%) and hospitals (26-29%) could have been of a great help. With respect to smoking cessation, all (100%) of the non-smoking physicians were involved in smoking-cessation counseling or stressing the health hazards of smoking, compared with only 50% of the smoking group (p < 0.001). Moreover, the smokers tended to underestimate the risks of several smoking-related health hazards and did not emphasize them when counseling patients. Major obstacles to advising smoking cessation were lack of counseling time (53-70%) and pessimism regarding the outcomes of their efforts (60%), while 8% of the internists and 14% of the surgeons believed that counseling was not part of their role. The authors conclude that physician smokers need to be encouraged in their efforts to quit by their colleagues and by members of their families. Quitting smoking might help them to develop an optimistic view of success in their cancer-prevention practices.

Increased serum levels of ghrelin at diagnosis mediate body weight loss in non-small cell lung cancer (NSCLC) patients.

OBJECTIVEnGhrelin is an orexigenic peptide implicated in body weight regulation, while cachexia is a multifactorial effect of non-small cell lung cancer (NSCLC) presented in patients with advanced disease. The aim of this study was to detect the role of ghrelin in cachexia and systemic inflammation of advanced NSCLC patients as well as its role as a diagnostic and prognostic tool.nnnMETHODSnGhrelin serum levels were measured in 101 inoperable NSCLC patients before receiving any therapy (75 patients with weight loss and 26 without weight loss) and 60 healthy control volunteers. Epidemiological, anthropometrical and laboratory data were assessed for all participants (patients and healthy volunteers).nnnRESULTSnNSCLC patients presented significantly higher ghrelin serum levels than healthy individuals, adjusted for sex, age and BMI (0.5+/-0.4 ng/ml vs. 0.4+/-0.3 ng/ml, P<0.001). NSCLC patients with weight loss presented significantly increased ghrelin serum levels (0.56+/-0.24 ng/ml vs. 0.52+/-0.44 ng/ml, P=0.017), compared to NSCLC patients without weight loss.nnnCONCLUSIONSnGhrelin serum levels are significantly increased in NSCLC patients, mainly in the subgroup of patients diagnosed with cachexia, indicating a possible implication in the pathogenesis of lung cancer. Further studies are needed to determine its potential role as predictive and prognostic marker.

A feasibility study of 1-h paclitaxel infusion in patients with solid tumors.

Abstractu2003The optimal schedule for paclitaxel administration has not yet been determined. This phase I/II study was carried out to evaluate the safety of paclitaxel administration by 1-h infusion in the outpatient setting. A total of 43 patients with advanced pretreated malignancies (18 breast, 18 ovarian, and 7 non-small-cell lung cancers) received at least 2 cycles of paclitaxel given at 175 mg/m2 in a single dose by 1-h i.u200av. infusion. This protocol was repeated every 21 days. All patients were premedicated as follows: promethazine given i.u200am. at 50 mg, dexamethasone given at 16 mg in 250 ml normal saline by i.u200av. infusion for 20 min and ranitidine given i.u200av. at 50 mg in 250 ml normal saline over 15 min, all premedication being carried out 1 h before the paclitaxel infusion. In a total of 156 cycles, only 1 patient presented with a hypersensitivity reaction (grade 2 urticaria in 1 cycle) and another patient developed transient facial flushing (in 1 cycle; this was resolved by slowing of the infusion rate) on this schedule of paclitaxel administration. Other adverse side effects were usually mild and well tolerated. Alopecia was universal; myelosuppression was uncommon because our patients were supported with granulocyte colony-stimulating factor (G-CSF, lenograstim) given at 34 IU/day in the presence of a neutrophil count of <500 μl; neutropenia was seen in 50/156 (32%) cycles and was mild. Neurotoxicity was the most serious adverse effect, and all patients experienced mild to severe neuromuscular toxicity, mainly in the form of peripheral sensorimotor neuropathy and myalgias. In conclusion, 1-h paclitaxel administration is safe and reduces the duration of treatment, making its use more convenient and easy in the outpatient setting. A prospective comparison of 1-h versus 3-h paclitaxel infusion in terms of efficacy and toxicity is the subject of our current randomized study.

Sequential combination of paclitaxel-carboplatin and paclitaxel-liposomal doxorubicin as a first-line treatment in patients with ovarian cancer. A multicenter phase II trial.

Cisplatin or carboplatin plus paclitaxel is considered the standard first-line treatment in ovarian cancer. Attempts to maximize tumor cytoreduction with first-line chemotherapy by incorporating new promising agents led to sequential drug administration with two or three doublets. In the present study, we aimed to evaluate the activity and the tolerance of two sequential doublets (paclitaxel/carboplatin and liposomal doxorubicin/carboplatin) administered as first-line treatment in patients with FIGO III/IV ovarian cancer. Treatment consisted of four cycles of carboplatin (6 AUC) plus paclitaxel (175 mg/m2; PC regimen) followed by four cycles with carboplatin (6 AUC) plus liposomal doxorubicin (40 mg/m2; LD/C regimen) every 3 weeks. Forty-one patients in FIGO III or IV were enrolled. In an intention-to-treat analysis, 20 (49%) complete (CR) and 12 (29%) partial (PR) responses were achieved (overall response rate, ORR: 78%; 95% confidence interval, CI: 64.1–91.9%); with the PC regimen (164 cycles); 7 (17%) patients have stable (SD) and 2 (5%) progressive (PD) disease. The LD/C regimen (124 cycles) was administered in 36 (88%) patients because of 2 early deaths and 3 patient withdrawals. Three additional patients, 2 with PR and 1 with SD after PC chemotherapy) achieved a CR. Upon completion of the LD/C chemotherapy there were 18 (44%) patients with CR and 9 (22%) with PR (ORR = 66%; 95% CI: 64–92%). The median duration of response was 27 months and the median time to progression 20 months. The probability of 2-year survival was 67%. Grade 3 and 4 neutropenia was observed in 34 and 14.6% of the patients, respectively, during the PC regimen, while during the treatment with LD/C the percentages for grade 3 and 4 neutropenia were 44.4 and 19.4%, respectively. Febrile neutropenia occurred only in patients treated with the PC regimen (4.9%). The incorporation of liposomal doxorubicin in this sequential doublet schedule of first-line treatment of ovarian carcinoma created a feasible and active regimen. Prospective randomized studies are required to assess its efficacy on patient survival.