Long-term results of a pilot study on an intensive induction regimen for unresectable stage III non-small-cell lung cancer.

BACKGROUND: In 1995, we designed and carried out a pilot study on the combination of cisplatin + high dose epirubicin + vinorelbine with granulocyte-colony-stimulating factor support for the induction treatment of unresectable stage IIIAN2 and wet IIIB non-small-cell lung cancer. The present report concerns the long-term results. METHOD: Eligible patients received cisplatin, 75 mg/m(2), and epirubicin, 120 mg/m(2), on day 1, vinorelbine, 25 mg/m(2), on days 1 and 15, and granulocyte-colony-stimulating factor, 300 microg s.c., from days 3 to 12. The cycle was repeated every 3 weeks for 3 times. Subsequently, all the patients were re-evaluated for surgical resection. RESULTS: Twenty-six patients were enrolled: 21 males and 5 females; median age, 55 years (range, 31-64); median performance status, 90% (range, 80-100); 16 stage IIIA and 10 IIIB. After the 3 cycles, objective response was as follows: 2 complete (8%), 18 partial (69%), 5 no change (19%) and 1 progressive disease (4%). Ten patients were not operated (9 unresectable and 1 refusal) and received radiotherapy. Sixteen patients (61%) underwent surgery and 14 were completely resected (54%). After a median follow-up of 84 months (range, 12-120), the median overall progression-free survival was 17 months (range, 2-104+): 47 months for resected and 8 months for nonresected patients. The median overall survival was 40 months (range, 4-123+): 87 months for resected and 13 months for nonresected patients. One-year, 3-year and 5-year survival rates were 73%, 42% and 37%, respectively. CONCLUSIONS: These intensive cytotoxic regimen enabled us to obtain favorable long-term results in a selected series of inoperable stage III non-small-cell lung cancer patients.

Multimodal sequential approach in colorectal cancer liver metastases: hepatic resection after yttrium-90 selective internal radiation therapy and cetuximab rescue treatment.

Synchronous or metachronous liver metastases occur in up to one-third of patients with colorectal cancer and are associated with a poor prognosis. Many evidences have shown that surgical resection can be curative, with 5-year survival rates ranging from 37% to 50%, but many patients are ineligible for surgery because of multiple liver lesions, bilobar distribution of liver metastases, or the presence of widespread extrahepatic disease. The management of unresectable liver metastases includes many therapeutic options such as systemic chemotherapy, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90), targeted therapy, and surgery. These treatments can be integrated into a sequential multimodal approach to increase the resection rate. We present a case in which such an approach was put into practice. The favorable result suggests that SIRT, along with systemic chemotherapy and surgery, is a valid treatment option for unresectable colorectal liver metastases.

Does stent placement for advanced colon cancer increase the risk of perforation during bevacizumab-based therapy?

BACKGROUND & AIMS: Data on the safety of bevacizumab-based therapies for patients carrying a self-expandable metallic stent (SEMS) for occlusive colon cancer are lacking. We report 2 cases of colon perforation observed in our case series of patients with SEMS for occlusive colon cancer. METHODS: Patients with occlusive symptoms caused by colon cancer received a colonic stent under endoscopic and radiologic guidance. RESULTS: Over a 10-month period, 28 patients with occlusive colon cancer were treated with stent placement. The stent was placed as a bridge to surgery in 12 patients who were treated surgically within 4 to 78 days after the endoscopic procedures, without any stent-related complications. Seven patients did not receive any other antitumor treatment as a result of concomitant comorbidities. Nine patients with both primary tumor and metastatic lesions were treated with medical therapy. Over a median follow-up period of 131 days colonic perforation occurred in the 2 patients treated with a combination of capecitabine and oxaliplatin plus bevacizumab. CONCLUSIONS: Further studies are needed to clarify whether SEMS placement increases the risk of perforation caused by bevacizumab-based therapies.

Cancer chemotherapy near the end of life: the time has come to set guidelines for its appropriate use.

AIMS AND BACKGROUND: This study retrospectively analyzes the use of chemotherapy in patients who died of advanced cancer either after having been in care at the Medical Oncology Unit (MOU) of the University Hospital of Bologna, Italy, or after having been assisted in their terminal disease phase by the Bologna Oncological Hospice at Home (OHH) of the Associazione Nazionale Tumori (ANT) Italia Foundation. In the latter group, the prescription and delivery of chemotherapy had been performed by doctors of medical oncology departments other than the MOU. RESULTS: Between January 2003 and September 2005, 793 deaths of patients were recorded (MOU: 312; OHH: 481). At least one cycle of chemotherapy had been received by 445 patients (56.1%). The most common cancer types were lung cancer (26.7%), colorectal cancer (14.8%), and breast cancer (11.2%). At the time of the last chemotherapy (I-CT), the median age of the patients was 68 years (range, 22-98 years) and the median KPS was 70 (range, 40-100). The median interval between I-CT and death was 71 days (range, 1-1913 days). One hundred and one patients (22.7%) had received their I-CT in the last 30 days of their life, 86% of them having intermediately chemosensitive (71%) or chemoresistant (14%) tumors. The I-CT in the last month of life was first line in 56% of cases and consisted of costly new-generation drugs in 36.6% of cases. CONCLUSIONS: The study suggests the urgent need to lay down guidelines for the appropriate use of chemotherapy in advanced cancer patients with a short life expectancy.

18FDG-PET evaluation correlates better than CT with pathological response in a metastatic colon cancer patient treated with bevacizumab-based therapy.

Around 20-30% of patients with hepatic metastasis from colorectal cancer can undergo liver resection, but the increased response rate obtained with the addition of monoclonal antibodies to chemotherapy regimens could result in a higher rate of liver surgery. In this report we describe the case of a patient who underwent a liver resection after neoadjuvant treatment with capecitabine, oxaliplatin and bevacizumab and who achieved a complete pathological response of the liver metastasis. A preoperative CT scan demonstrated a partial response to the treatment while 18FDG-PET scan correctly evaluated the complete pathological response in the liver and detected an active interaortocaval lymph node metastasis. New specific studies are required to evaluate the imaging response in metastatic colorectal cancer patients especially after treatment with new, targeted agents.

Capecitabine plus oxaliplatin (xelox) versus protracted 5-fluorouracil venous infusion plus oxaliplatin (pvifox) as first-line treatment in advanced colorectal cancer: a GOAM phase II randomised study (FOCA trial).

UNLABELLED: This phase II randomised trial compares oxaliplatin plus protracted infusion of 5-fluorouracil (pviFOX) or oxaliplatin plus capecitabine (XELOX) in the first-line treatment of advanced colorectal cancer (ACRC). METHODS: From December 2001 to March 2005, 118 patients were randomised to arm A (pviFOX: pvi5-FU by a central venous catheter 250 mg/m2/daily d1-21+oxaliplatin 130 mg/m2 d1 q3w) (56 pts) or arm B (XELOX: capecitabine 1000 mg/m2 po bid d1-14+oxaliplatin at the same schedule) (62 pts). RESULTS: Patient characteristics were well-balanced between the two arms. Median number of complete cycles was six. The objective responses were: CR 1 (1.7%) and 3 (4.8%), PR 26 (46.4 %) and 24 (38.7%), SD 13 (23.2%) and 20 (32.3%), P 13(23.2%) and 10 (16.1%), not evaluable 3 (5.4%) and 5 (8.1 %) in arms A and B, respectively; the CR+PR rate was 48.2% (95% confidence limits 34.6%-61.9%) versus 43.5 % (31.0%-56.7%). Median TTP was 7 versus 9 months, respectively. About 50% of the patients with symptoms or low performance status at baseline experienced improvement without major differences between the two arms. G3-4 diarrhoea was observed in 14.0% versus 8.2%, G3 stomatitis in 3.7% versus 0, and G3 neurotoxicity in 18.5% versus 24.6% in arms A and B, respectively. Eight patients in arm A (14.8%) had venous line problems that obliged the temporary suspension (six cases) or stopping (two cases) of the 5-FU infusion. CONCLUSION: Both pviFOX and XELOX are effective and safe first-line treatments for patients with ACRC. By avoiding intravenous (i.v.) administration by a central catheter, XELOX is favoured in clinical practice.

Does biomolecular characterization of stage II/III colorectal cancer have any prognostic value?

As new improvements in the treatment of colorectal cancer have become available, it has become important to understand the benefits of new therapies or the deleterious effects stemming from the increased risk of toxicity. In particular, a more rational approach to adjuvant chemotherapy for patients with stage II/III disease should be defined by understanding which patients have a higher recurrence risk. Many studies have investigated several molecular markers, but none has been definitively associated with patient outcome. We present a review of studies that have evaluated the immunohistochemical correlation between expression of some biomarkers, such as thymidylate synthase, p53, Ki-67, Bcl-2, and microsatellite instability status expressed by Mut-L homologue 1 and Mut-S homologue 2 proteins, and the prognosis of patients with stage II/III colorectal cancer. We have evaluated studies in which > or = 100 patients were involved in an effort to ensure a representative study group. The only biomarker likely to have a prognostic value is microsatellite instability status, which correlated with a better prognosis.

Planned sequence of gemcitabine followed by vinorelbine in the treatment of elderly patients with advanced non-small cell lung cancer.

BACKGROUND: The rationale for planned sequential chemotherapy is based on the principle that sequential administration of non-cross-resistant cytotoxic agents has the advantage of eliminating additive toxicity and permitting the delivery of full doses of each drug. At present, there is a lack of data on the results of planned sequential single agent administration in elderly patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to explore the possibility of increasing the time-to-progression (TTP) by a 1.5 factor in comparison with the historical results of monochemotherapy with a first-line planned sequential administration of gemcitabine (GEM) and vinorelbine (VNR). PATIENTS AND METHODS: GEM 1000 mg/m2 was administered intravenously (i.v.) for 30 min on days 1, 8 and 15 and recycled on day 28 for a total of 3 cycles. Independently of response, VNR was administered i.v. as a bolus at a dose of 25 mg/m2 on days 1, 8 and 15 of a 28-day cycle. VNR treatment was continued until disease progression or intolerance. RESULTS: Fifty-two consecutive patients, with a median age of 76 years (70-85), affected by locally advanced (35%), metastatic (54%) or recurrent (11%) NSCLC were enrolled. The overall best objective response was 3.8% CR, 19.2% PR, 32.7% SD, 23.1% disease progression and 21.2% not evaluable. Both drugs were well tolerated. The median TTP was 6 months (95% confidence limits 4-8), the median overall survival was 10 months (95% confidence limits 6-14) and the one-year survival rate was 42%. CONCLUSION: The planned sequential administration of GEM and VNR suggests that the TTP can be increased with the use of the 2 single agents in elderly patients with locally advanced or metastatic NSCLC.

Gemcitabine plus mitoxantrone and prednisone in the palliative treatment of hormone-resistant prostate cancer (HRPC): A phase II study (GOAM 01.01 study).

BACKGROUND: The present exploratory phase II study was performed to evaluate the activity and tolerability of adding a second agent (gemcitabine) to the well-tolerated mitoxantrone/prednisone regimen in patients with locally advanced or metastatic prostate cancer no longer responsive to hormonal treatment. PATIENTS AND METHODS: Forty-three patients with hormone-refractory prostate cancer (HRPC) were included in the study from May 2000 to April 2004. Their median age was 71 years (range, 56-81) and their median Karnofsky performance status (KPS) was 90 (range, 70-100). The treatment schedule consisted of intravenous (i.v.) mitoxantrone (8 mg/m2 on day 1), i.v. gemcitabine 800 mg/m2 on days 1 and 8, recycled every 21 days and oral prednisone administered at a dose of 10 mg per day. Hormonal treatment with LHRH was continued in all patients. Up to six cycles of treatment were planned in the absence of progressive disease. RESULTS: Sixteen patients had measurable disease (six patients only measurable disease, ten patients bone disease plus measurable disease) and 27 patients had only bone disease. Concerning the PSA levels, a partial response (PR) was observed in 15 patients (38%), stable disease (SD) in 16 patients (41%) and progressive disease (PD) in eight patients (21%). The objective response was evaluable in 16 patients; one patient was not evaluable because he had received only one cycle. Ten patients (63%) had SD and five patients (31%) PD. In the ten evaluable patients with objective SD, depending upon the PSA response, three PR, six SD and one PD were observed. Among the five patients who progressed, three PD and two SD were observed as a PSA response. Pain remission was recorded in 15/41 patients (36%) and the KPS remained stable in most patients. The median overall survival was 15 months (range, 1-41) (95% CI: 10-20 months). The 1-year survival rate was 61%. Hematological toxicity was mild: G 3-4 neutropenia was observed in five (12%) patients. There were no neutropenic, fevers. No significant non-hematological toxicity was observed. CONCLUSION: The mitoxantrone, gemcitabine and prednisone combination, in accordance with the present regimen, was feasible, had a palliative effect, good tolerance and antitumor activity. Nonetheless, our results do not seem to be superior to those previously described for mitoxantrone plus prednisone.

Solitary Internal Mammary Lymph Node Metastases Detected by F-FDG-PET/CT in Ovarian Cancer.

Internal mammary lymph nodes as solitary site of recurrent ovarian cancer have not been previously described. In this case report, 3 cases of late and very late isolated recurrence in internal mammary lymph nodes are presented. (18)F-FDG-PET/CT allowed the diagnosis which was suspected by the increase of the serum CA-125 level in 2 out of 3 cases. Local treatment, consisting of surgery (in 2 patients) and radiation therapy (in 1 patient), permitted an optimal long-term disease control.

Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer patients treated with neo-adjuvant chemotherapy: determination by array and kinetic PCR in fresh tissue biopsies.

Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the context of a neo-adjuvant chemotherapy trial. Study participants had epithelial ovarian or peritoneal carcinoma unsuitable for optimal upfront surgery and were treated with neo-adjuvant platinum-based chemotherapy before surgery. RNA was isolated from frozen tumour biopsies before treatment. RNA expression of ESR1 was determined by microarray and reverse transcriptase kinetic PCR technologies. The prognostic value of ESR1 was tested using univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival statistics and the log-rank test. ESR1 positively correlates with proliferation markers and histopathological grading. ESR1 was a significant predictor of survival as a continuous variable in the univariate Cox regression analysis. In multivariate analysis, elevated baseline ESR1 mRNA levels predicted prolonged progression-free survival (P=0.041) and overall survival (P=0.01) after neo-adjuvant chemotherapy, independently of pathological grade and age. We conclude that pretreatment ESR1 mRNA is associated with tumour growth and is a strong prognostic factor in ovarian cancer, independent of the strongest clinical parameters used in clinical routine. We suggest that ESR1 mRNA status should be considered in order to minimize possible confounding effects in ovarian cancer clinical trials, and that early treatment with anti-hormonal agents based on reliable hormone receptor status determination is worth investigating.