Maintenance chemotherapy or not in ovarian cancer stages IIIA, B, C, and IV after disease recurrence.

PURPOSE: Ovarian cancer may have a high percentage of residual disease after chemotherapy. It is questionable whether second or more lines of chemotherapy are needed in patients with slow-growing residual disease. In the present trial we compared the median survival of patients with residual or recurrent disease who received 1-2 lines of chemotherapy with those who received 3-9 lines. METHODS: Two hundred and five patients with advanced stage IIIA, B, C and IV ovarian cancer were divided into two groups based on the number of chemotherapy lines they received. All patients had prior first-line chemotherapy; the criteria for recruitment in the study were: a) residual or recurrent disease and b) failure to respond to first-line therapy. Group A included patients who received 1 or 2 lines of chemotherapy and group B, 3-9 lines. RESULTS: The median survival of group A was 76 months and of group B 53 months (p<0.001). Complete response (CR) was observed in 80 out of the 193 7lpar;41.45%) evaluable patients, partial response (PR) in 37 (19.17%), stable disease (SD) in 54 (27.987percnt;) and progressive disease (PD) in 22 (11.40%) patients. CONCLUSION: In ovarian cancer patients with advanced disease, multiple chemotherapy lines (3=9) offer no advantage over 1 or 2 lines, with respect to overall survival.

Liposomal cisplatin dose escalation for determining the maximum tolerated dose and dose-limiting toxicity: a phase I study.

BACKGROUND: The aim of the present trial was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of liposomal cisplatin (lipoplatin) using nephrotoxicity, gastrointestinal toxicity and myelotoxicity as the main adverse reactions. PATIENTS AND METHODS: Lipoplatin, a liposomal formulation of cisplatin was first tested as monotherapy starting at a dose of 125 mg/m(2) and escalating up to 350 mg/m(2). Lipoplatin was then escalated in combination with paclitacel starting at a dose of 100 mg/m(2) escalating up to 250 mg/m(2) for the former and 100 mg/m(2) escalating up to 175 mg/m(2) for the latter. RESULTS AND CONCLUSION: The present trial determined the DLT for lipoplatin monotherapy at 350 mg/m(2) and the MTD at 300 mg/m(2); for lipoplatin-paclitaxel combination therapy, the DLT was 250 mg/m(2) for lipoplatin and 175 mg/m(2) for paclitaxel whereas the MTD was 200 mg/m(2) for lipoplatin and 175 mg/m(2) for paclitaxel.

Lung carcinoid tumor biology: treatment and survival.

A carcinoid tumor is a rare malignant disease which can be cured when localized and treated by surgery. Chemotherapy is not effective, and somatostatin is used for palliation. Rarely is the disease aggressive, and thus does not contribute to a shortening of patient survival. The aim of this study was to define the treatment and survival of patients with primary lung carcinoid tumors. Forty-three patients (26 males, 17 females; median age 43 years, range 11-73 years), from 1993 to 2007, were included in this study. All patients had histologically confirmed carcinoid tumors. The site of the disease at diagnosis was the lung in all 43 patients. All patients underwent surgery which involved mainly typical or sleeve lobectomy. Eight patients had a pneumonectomy. One patient had the primary tumor excised for palliation as there were metastases in the liver. Somatostatin palliative treatment was administered to 4 patients; 1 with liver and 3 with lung recurrence. Two of the 43 patients died within 2 years after surgery. The median survival was not reached as all patients, apart from 2, were alive after a median follow-up of 5 years (mean survival 159 months). As a rule, a carcinoid tumor is an extremely slow-growing disease with some rare exceptions. All of our patients had primary lung disease. All, apart from 2, were alive at the end of the study, and 93% were without recurrence for a duration of 6 months to 13 years. The patients with liver metastases who underwent no specific treatment had a median survival as long as 8 years.

Capecitabine (Xeloda) as monotherapy in advanced breast and colorectal cancer: effectiveness and side-effects.

BACKGROUND: Capecitabine (Xeloda) is a fluoropyrimidine which is transformed to 5-fluorouracil (5-FU) at the tumor site. The aim of the present study was to estimate the efficacy of this agent in pretreated patients with advanced breast and colorectal cancer, and to determine the response rate and adverse reactions. PATIENTS AND METHODS: Forty-two patients (median age 65 years, range 27-80 years), 24 with breast cancer, 17 with colorectal cancer and one with a pancreatic islet tumor were included. Capecitabine was administered at a dose of 1200 mg/m2 twice daily for two weeks every 21 days. No other agent or supportive treatment was planned. RESULTS: A partial response was observed in 29.16% of the patients with breast cancer and in 11.76% of the patients with colorectal cancer. Stable disease was observed in 58.33% and 70.59% of the breast cancer and colorectal patients, respectively. Adverse reactions were very mild with respect to myelotoxicity and GI tract toxicity. Grade 3 hand-foot syndrome was observed in three patients (7.14%). Hypertriglyceridemia, an unusual side-effect, was observed in 5/12 patients who were tested for serum cholesterol triglycerides. CONCLUSION: Capecitabine is a well tolerated treatment with low toxicity, rendering a partial response in 29.16% and 11.76% of patients with breast and colorectal cancer, respectively.

Adjuvant chemotherapy for colon cancer: evidence on improvement in survival.

Clear progress has been made in the adjuvant treatment of colon cancer. Until very recently, the absolute benefit for survival obtained with the administration of 6 months' FU/LV compared with control was about 6%. Fluoropyrimidines have been shown to be at least as active and can replace intravenous FU/LV in stage III colon cancer. Based on the results of the MOSAIC and NSABP C-07 trials, the addition of oxaliplatin to FU/LV improves disease-free survival and FOLFOX for 6 months can be recommended as adjuvant treatment for patients with stage III colon cancer. The benefit of adjuvant chemotherapy in stage II disease is limited and it should be proposed in patients with high-risk features. Adjuvant treatment of colon cancer improving and the use of genetic/molecular markers with the new targeted therapies may further improve survival.

Weekly administration of topotecan-paclitaxel as second-line treatment in ovarian cancer.

PURPOSE: To investigate the weekly administration of topotecan combined with paclitaxel in pretreated advanced ovarian cancer patients; our objectives were to determine efficacy, toxicity and survival. METHODS: The chemotherapy agents, topotecan and paclitaxel were administered on a weekly basis for 3 consecutive weeks, every 28 days. The plan was to give three courses (each course included three once-weekly infusions). The dose of topotecan was 1.75 mg/m(2) and of paclitaxel 70 mg/m(2). RESULTS: From January 2004 until January 2006, 45 patients were enrolled in this multicenter trial; 44 patients were evaluable for response and toxicity. The median age was 60 years old (range 39-82 years) and performance status was 0-2. Thirty-nine patients were in stage III and 5 in stage IV. All patients had been pretreated with carboplatin or cisplatin in combination with paclitaxel. Complete and partial responses were seen in 39% of the patients, stable disease in 43% and progressive disease in 18%; median survival time was 9 months, range 2-24+ months, (95% CI: 7.9-10.2). There was a notable absence of grade 3 toxicity except for neutropenia in 11% of the patients. CONCLUSION: The combination of topotecan and paclitaxel administered on a weekly basis is a well-tolerated chemotherapy schedule. The response rate of 39% is quite high for patients with pretreated ovarian cancer.

Surgical management in lung metastases from colorectal cancer.

BACKGROUND: Colorectal cancer is a non-aggressive slow-growing disease. Surgery is often considered for the management of metastases. Chemotherapeutical agents may offer tumor reduction but radical tumor remission can only be achieved by surgery. The aim of the present study was to show the evolution of patients with lung metastases from colorectal cancer, treated with surgery. PATIENTS AND METHODS: Five hundred and seventy-nine (male 327, female 252, median age 60 years [range 30-87 years], disease stage IV) patients with colorectal cancer were evaluated. Histology showed adenocarcinoma with 94% moderate differentiation. Sixty-six patients (11.40%) had only lung metastasis (single or multiple deposits). Of these 66 patients, 57 were treated with surgery (pneumonectomy, lobectomy or nodule excision) and in 52/57 (91.23%) the tumor was removed. RESULTS: In 29 patients (50.88%) the disease recurred 8 months after surgery, at the earliest; however, no recurrence was observed in 28 patients (49.12%) during 2-8 years of follow-up after the operation. Five-year survival was 32.69%. CONCLUSION: Metastectomy of lung metastasis from primary colorectal cancer may achieve long-term survival without recurrence in a large percentage of patients.

Second-line chemotherapy in small cell lung cancer in a modified administration of topotecan combined with paclitaxel: a phase II study.

PURPOSE: Our main objective was to investigate the response rate in pretreated patients with small cell lung cancer (SCLC) who received a weekly administration of topotecan and paclitaxel; our secondary objectives were to assess toxicity and survival. METHODS: Topotecan 1.75 mg/m2 was combined with paclitaxel 70 mg/m2; these cytotoxic agents were administered once every week (day 1) for 3 consecutive weeks (one cycle), and repeated every 28 days (three infusions per cycle) for a minimum of three cycles. RESULTS: Forty-five patients were enrolled, 41 of whom were evaluable for response and toxicity. The median number of cycles was two (range 1-6). Eleven/forty-one (26.83%) patients responded: one complete response and ten partial responses; the median duration of response was 4 months (range 2-8 months); the median overall survival was 7 months (95% CI: 4.2-9.8). Myelotoxicity was the most common adverse reaction (grade 3 neutropenia in 19.5% of the patients and grade 4 in 7.32%). Non-hematologic toxicities varied from 2.44% to 9.76%. No patient had to stop treatment due to toxicity. CONCLUSION: Topotecan combined with paclitaxel, given on day 1 on a weekly basis, produced a response rate of 26.83% in pretreated patients with SCLC. Myelotoxicity, particularly neutropenia, was the main adverse reaction, but in a minority of patients.

Primitive neurectodermal tumors: a case of extraosseous Ewing's sarcoma of the small intestine and review of the literature.

This is a review of extraosseous Ewing's sarcoma (ES) which includes a new, extremely rare case. The literature was examined with respect to determining the locations of extraosseous ESs, the incidence per site and in total and the criteria which confirm the similarity between extraosseous and osseous ES. ES sites were detected in several organs and tissues, mainly in the trunk, extremities and the retroperitoneal region. Studies confirmed that osseous and extraosseous ES are identical chromosomally and histologically. ES of the small intestine, described here, has not been previously documented in the literature. Along with the other different documented sites, a new location of primary extraosseous ES is also reported here.

Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study.

PURPOSE: This is a phase II study where a novel chemotherapy combination was tested in pre-treated breast cancer patients: docetaxel and irinotecan have already been established as agents for breast and colorectal cancer, respectively. METHODS: Forty-eight (median age 54 years, range 26-77 year) patients, all evaluable, were enrolled. All patients had been pre-treated with anthracycline-combined chemotherapy, 30 of whom were also treated with paclitaxel and 2 with docetaxel. World Health Organization (WHO) performance status was 0-2. The dominant metastasis was in the liver (54.17%), in the lungs (27.08%), in soft tissues (12.50%) and in the skeleton (6.25%). Treatment involved irinotecan infusion 200 mg/m(2) for 90 min and docetaxel infusion 80 mg/m(2) for 90 min, repeated once every 3 weeks. RESULTS: Twenty-five (52.08%, 95% confidence interval [CI] 37.95-66.21) patients showed responses: 3 complete (6.25%, 95% CI 0-13.05) and 22 (45.83%, 95% CI 31.74-59.92) partial; the most responsive metastases were observed at the liver site (53.85%). Grade 3 and 4 neutropenia was observed in 18 patients (37.50%); 14 (29.17%) patients developed anaemia and three (6.25%), thrombocytopenia. Concerning non-haematologic toxicity, alopecia and fatigue were common; grade 3 diarrhea was observed in only one (2.08%) patient. CONCLUSION: The irinotecan-docetaxel combination produces quite a high response rate in pre-treated advanced breast cancer patients.

Treatment of non-small cell lung cancer with gefitinib ('Iressa', ZD1839): the Greek experience with a compassionate-use program.

This is a retrospective analysis of 150 patients with advanced non-small cell lung cancer who had failed prior treatment or were unfit for chemotherapy and were treated with oral gefitinib ('Iressa', ZD1839; AstraZeneca) 250 mg/day. Thirty-two patients who received gefitinib for 3 weeks or less were not included in the analysis. For the remaining 118 evaluable patients, the mean age was 63.1 years; most patients had received prior chemotherapy (97.5%), Eastern Cooperative Oncology Group performance status scores 0-2 (97.4%) and stage IV disease (64.4%). The majority were symptomatic (84.6%). Disease control was observed in 30 patients (25.4%), of whom five had a partial response and 25 had stable disease; 18 (15.3%) were not evaluable. Median duration of treatment was 29.9 weeks in responding patients and 11.5 in patients with progressive disease (p<0.0001). Median overall survival was 7.3 months (15.2 months for disease control) and median progression-free survival was 3.2 months. Gefitinib was well tolerated, with grade 3/4 skin rash and diarrhea seen in 2.5 and 4.2% of patients, respectively. Clinical benefit was evaluated using questionnaires before and following treatment with gefitinib. In 82 patients with completed questionnaires, evaluation revealed symptom improvement in 40.1% and improvement in general feeling in 31.4%. Epidermal growth factor receptor (EGFR) analysis found that efficacy did not correlate with tumor EGFR overexpression. Therefore, in this retrospective analysis, gefitinib treatment provided disease control in 25% of patients who derived significant palliative benefit.

Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer: a randomized phase III trial.

PURPOSE: This randomized phase III trial of advanced or metastatic non-small-cell lung cancer (NSCLC) was designed to compare a standard treatment such as carboplatin (CRP)-paclitaxel (PCT) with a new combination, vinorelbine (VRL)-PCT-two agents acting in microtubules. PATIENTS AND METHODS: Three hundred and sixty patients (stage IIIa, IIIb and IV) were included and evaluated for response rate, survival and toxicity. Arm A patients were treated with the control combination of CRP 6 AUC and PCT 175 mg/m(2) repeated every 3 weeks for six cycles, and arm B with the investigational combination of VRL 25 mg/m(2) and PCT 135 mg/m(2) repeated every 2 weeks for nine cycles. The patients were well balanced with respect to gender, disease stage and performance status. Arm A received 849 cycles (mean 4.59 per patient) and arm B 951 cycles (mean 5.39 per patient). RESULTS: Complete and partial response rates were 45.95% and 42.86% for arms A and B, respectively. Median survival was 11 and 10 months, 1-year survival 42.7% and 37.85% and 2-year survival 10.12% and 19% for arms A and B, respectively. Toxicity was similar in all patients, except for neutropenia, which was significantly greater in arm B. CONCLUSIONS: PCT combined with VRL produces similar (non-significant) response rates, survival and toxicity (except for neutropenia, as noted above) to standard CRP-PCT treatment in untreated advanced-stage NSCLC.

Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study.

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine (GEM) combined with capecitabine (CAP) in untreated patients with inoperable or metastatic pancreatic cancer. PATIENTS AND METHODS: Fifty-three patients with pancreatic cancer (85% stage IV) were enrolled. Patients were treated with GEM 1000 mg/m2 on days 1 and 8 and CAP 1300 mg/m2 per day PO (per os), divided into two equal doses on days 1-14, in 21-day cycles. RESULTS: In an-intention-to-treat analysis, 10 (18.9%) objective partial responses were achieved (95% confidence interval 8.33% to 29.4%). Twenty-two (42%) patients had stable disease and 15 (28%) had progressive disease. The median response time was 3 months (range 1.5-7.0) and the median time to tumor progression was 6.5 months (range 3.5-15.5). Median overall survival time was 8 months (range 1.0-15.5) and 1-year survival was 34.8%. Pain improvement during treatment was observed in 23 of 43 (53%) patients, and eight of 18 (44%) patients who had been receiving opioids discontinued their use. Weight gain was observed in 12 of 33 (36%) patients. Grade 3 anemia occurred in five (9%) patients and grade 3-4 thrombocytopenia occurred in three (6%). Grade 3-4 neutropenia occurred in 13 (25%) and five (9%) patients, respectively, and two (4%) developed febrile neutropenia. Non-hematological toxicity was mild. CONCLUSION: In patients with pancreatic cancer, the combination of GEM with CAP is an active and well tolerated regimen that merits further evaluation in prospective randomized studies.

Treatment of pancreatic cancer with a combination of irinotecan (CPT-11) and gemcitabine: a multicenter phase II study by the Greek Cooperative Group for Pancreatic Cancer.

BACKGROUND: The efficacy and toxicity of gemcitabine (GEM) and irinotecan (CPT-11) is evaluated in previously untreated patients with inoperable or metastatic pancreatic cancer. PATIENTS AND METHODS: From January 1999 to July 2001, 60 patients with pancreatic cancer (85% stage IV) were enrolled in a two-step extended phase II trial. Patients were treated with gemcitabine (1,000 mg/m2 on days 1 and 8) and CPT-11 (300 mg/m2 on day 8) in cycles of 3 weeks. No prophylactic use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was initially planned. RESULTS: In an intention-to-treat analysis one (1.7%) complete and 14 (23.3%) partial responses were achieved [objective response rate (ORR) 24.7%; 95% confidence interval 14.04% to 35.96%]. Twenty-two (36.7%) and 23 (38.3%) patients had stable and progressive disease, respectively. The median duration of response was 5 months, the median time to tumor progression (TTP) was 7 months and the median overall survival 7 months. One-year survival was 22.5%. Pain improvement and asthenia during treatment were observed in 45% and 43% of patients, respectively; weight gain occurred in 19.5% of patients. Grade 3 anemia occurred in three (5%) patients who required transfusion of six packed red blood cell (RBC) units. Ten (16.7%) additional patients with grade 2 anemia were treated with recombinant erythropoietin. Grade 3 thrombocytopenia occurred in seven (11.7%) patients and grades 3 and 4 neutropenia in 27 (45%). Ten patients developed febrile neutropenia, two of whom died due to sepsis. Prophylactic use of rhG-CSF was eventually required in 93 (28.3%) of 329 administered cycles. Other toxicities were mild. CONCLUSIONS: The combination of gemcitabine and irinotecan is an active chemotherapy regimen against pancreatic cancer with a 25% ORR. Toxicity was acceptable for the great majority of patients but with a high percentage of hematopoietic growth factor administration.

Paclitaxel and carboplatin in pretreated advanced gastric cancer: a phase II study.

In the present study, the combination of paclitaxel and carboplatin was applied in the treatment of gastric carcinoma. This cytotoxic combination has been an effective regimen with acceptable toxicity in ovarian, lung and head and neck cancers. We evaluated 47 patients (37 male, 10 female), all with advanced disease and all having undergone prior chemotherapy treatment. All patients had disease progression or no response to the prior treatment. Forty-four patients had undergone a previous gastrectomy for gastric adenocarcinoma and 3 patients were inoperable at diagnosis. Paclitaxel 175 mg/m2 was administered as a three-hour infusion, followed by carboplatin 5 AUC infused for 90 min. Thirteen (27.66%) patients showed partial response with a median survival of 10 months; 3 (6.38%) patients showed minor response and 13 patients, stable disease with clinical benefit. The median survival of patients with minor response and disease stability was 6 months. Eighteen (38.29%) patients had disease progression with a median survival of 3 months. It appears that in advanced cancer patients, the paclitaxel-carboplatin combination is an effective second-line treatment, resulting in partial response and disease stability in 61% of patients as well as in a prolongation of median survival.

Angiogenesis and apoptosis-related protein (p53, bcl-2, and bax) expression versus response of gastric adenocarcinomas to paclitaxel and carboplatin chemotherapy.

The role of angiogenesis and apoptosis-related proteins in defining response to chemotherapy is poorly understood. We examined the microvessel density (MVD) and the expression of p53, bcl-2, and bax proteins in a series of 28 locally advanced gastric adenocarcinomas, treated with paclitaxel and carboplatin. A strong cytoplasmic reactivity in more than 10% of cancer cells was recorded in 25% of cases for p53 protein, and in 14% and 64% of cases for bcl-2 and bax proteins, respectively. Microvessel density was assigned in three categories: low (<35), medium (35-60), and high (>60). Tumors of medium MVD showed a significantly higher response rate compared with those of high or low MVD (p = 0.01 and 0.001, respectively), and prognosis was significantly better in this group of patients with medium MVD tumors (p < 0.02). Loss of bax protein expression was somewhat more frequent in tumors resistant to chemotherapy, but this difference was not of statistical significance. Nuclear p53 reactivity was associated with higher MVD (p = 0.02). The expression of p53 and bcl-2 did not influence the outcome of treatment. The present study suggests that although apoptosis-related proteins may have a role in defining response to taxanes, parameters related to tumors' vasculature, such as drug availability or angiogenic tissue regeneration, may be equally important.

Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: a phase II study of the Greek Cooperative Group for Pancreatic Cancer.

PURPOSE: To evaluate the tolerance and efficacy of front-line docetaxel plus gemcitabine treatment in patients with inoperable pancreatic cancer. PATIENTS AND METHODS: Fifty-four patients with locally advanced or metastatic pancreatic cancer were enrolled. Gemcitabine (1000 mg/m2) was administered on days 1 and 8 and docetaxel (100 mg/m2) on day 8, every three weeks; rh-G-CSF (150 ig/m2 s.c.) was given prophylactically on days 9-15. RESULTS: Seven (13%) patients achieved partial response and 18 (33%) stable disease (intent-to-treat). The median duration of response was 24 weeks, time to tumour progression 32 weeks, and overall survival 26 weeks. Performance status was improved in 33% of patients, pain in 43%, asthenia in 16%, weight gain in 28% and appetite in 27%. Grade 3-4 neutropenia occurred in 17 (31%) patients and grade 3-4 thrombocytopenia in four (4%). Six (11%) patients developed febrile neutropenia and one of them died from sepsis. CONCLUSIONS: This combination is a relatively well-tolerated out-patient regimen for patients with inoperable pancreatic cancer.

Merkel cell carcinoma: a case series of twelve patients and review of the literature.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumor of the skin. MATERIALS AND METHODS: A retrospective analysis of 12 cases of MCC diagnosed and treated over a 14-year period. RESULTS: Seven females and 5 males, with a median age of 72 years and MCC of the face (5), trunk (1) and extremities (6), were studied. The stage was I in 2 cases and II in 10. Eight patients had surgery, two surgery and chemotherapy and two chemotherapy only. The last two patients died of disease after 10 and 16 months. Three patients suffered locoregional recurrence after 4, 6 and 24 months and three were lost to follow-up after 8, 9 and 24 months while disease-free. Two disease-free patients died of unrelated causes after 4 and 48 months, while three were alive and well after 24, 48 and 84 months. The three relapsing patients received chemotherapy in addition to local radiation in one case. One is alive and well, the other alive with disease and the third died of disease after 84, 107 and 10 months, respectively. CONCLUSION: MCC often recurs locally. Surgery is the treatment of choice, while radiotherapy is important for local control. Chemotherapy produces responses in the neoadjuvant setting or after relapse.

Paclitaxel combined with cis-platin as second-line treatment in patients with advanced non-small cell lung cancers refractory to cis-platin.

We combined paclitaxel with cis-platin as second-line treatment in patients with non-small cell lung cancer (NSCLC) who had previously undergone first-line therapy with cis-platin combined with cytotoxic drugs other than taxanes. The aim was to evaluate the effect of this cytotoxic combination in patients with refractory tumour to cis-platin. All 36 patients in the study population were evaluable for toxicity and 35 for response. Nine patients were stage IIIa, 15 IIIb and 12 IV. Prior treatment involved cis-platin plus vindesine and epirubicin or vinblastine and mitomycin-C; second-line treatment involved cis-platin (90 mg/m2) and paclitaxel (175 mg/m2), administered once every 3 weeks with 2-6 courses per patient. Partial response (40%) was obtained in 14 patients, 8 of whom had achieved minor response or stable disease after first-line treatment. Response duration was a minimum of 3 months. Toxicity was tolerable; only neurotoxicity was grade II in 16.7% of the patients. On the basis of our results, paclitaxel can be recommended as a very effective cytotoxic drug for NSCLC patients.