A new and safe device for minimally invasive saphenous vein harvesting: results after 100 cases.

PURPOSE: : The saphenous vein is the most commonly used bypass conduit for coronary surgery. Endoscopic harvesting techniques are associated with significant reduction of wound complications but are time-consuming and expensive. The authors developed a device to perform minimally invasive harvesting of the saphenous vein-rapidly, inexpensively, and safely. DESCRIPTION: : Patients hospitalized for isolated CABG (n = 134) participated in the study. Each vein had been harvested through the use of our minimally invasive system. EVALUATION: : The veins were harvested in 130 cases; 378 vein samples were collected for pathology study, with complete integrity of the vein as the result of the "no touch" technique with the device. This integrity could be very important for the long-term patency of the vein graft. After surgery, there were no wound dehiscences, infections, or major hematomas. There was 1 case (0.76%) of superficial hematoma and 3 cases (2.30%) of lymphoceles. CONCLUSIONS: : Although commercial disposable systems are now available to allow minimally invasive harvesting of the saphenous vein, the authors think that harvesting the greater saphenous vein with the cylinder steel device is easy to learn can be used safely and at much-reduced costs.

Safety of long-term administration of bisphosphonates in elderly cancer patients.

BACKGROUND: To evaluate the effectiveness and tolerability of the long-term treatment bone metastases with pamidronate in older patients. MATERIALS AND METHODS: Twenty-two ambulatory patients aged 70 or older were included in the study. The median age was 73 (range 70-77). Ten patients (46%) were affected by breast carcinoma, 7 (32%) by prostate carcinoma and 5 (22%) by multiple myeloma. Nine (40%) patients presented co-morbidity. All of the patients presented at least one metastatic lytic bone lesion measuring 1 cm or more in diameter; the median lesion number was 2 (range 1-4). Hormonal therapy or chemotherapy regimen, were allowed as clinically required. Patients were treated with a fixed dose of sodium pamidronate, 90 mg in 3 h infusion every 4 weeks. RESULTS: Partial response was shown in 6 (28%) patients, stable disease in 11 (50%), and progression (PD) in 5 (22%). 2 out of 5 patients with PD presented skeletal-related events (SREs) such as bone fracture. The median treatment duration was 19 months. The treatment was well tolerated; in 5 patients (23%) a GI fever was observed, in 3 patients (18%) G1 nausea, and in 3 patients (14) G1 diarrhea. Two cases (9%) of acute renal insufficiency (creatinine 1.7 and 1.6 mg/dl), and 3 cases (14%) of hypocalcemia (7.6, 7.5 and 7.8 mg/dl) were also registered. The renal dysfunction was reversible and without consequence. CONCLUSION: Our experience suggests that the bisphosphonates long-term administration is useful and did not cause significant side effects in elderly subjects. Low-grade pyrexia, nausea/vomiting, acute/reversible renal dysfunction and hypo-calcemia were the most frequent side effects reported. However, they were of low grade and in most cases, did not require dose modifications and/or hospitalization.

Vinorelbine and prednisone in older cancer patients with hormone-refractory metastatic prostate cancer. A phase II study.

AIMS AND BACKGROUND: Prostate cancer is a common disease in older men. Since it is hormone resistant, no treatment may improve survival. In patients with hormone-refractory prostate cancer, clinical benefit is an important treatment end point. STUDY DESIGN: This study evaluated the efficacy and toxicity of a vinorelbine and prednisone combination in hormone-refractory prostate cancer patients. Vinorelbine was administered at the dose of 25 mg/m2 on days 1 and 8, every three weeks; prednisone was administered orally at the dose of 12 mg/day. Thirty consecutive patients, 65 years or older, with progressive (PSA increase or increase in bidimensionally measurable lesion) metastatic prostate adenocarcinoma were enrolled. Four patients (13%) had a partial response and 14 (46%) stable disease. Time to progression for the entire group was 4.5 months (range, 2-13) and 7.5 months for the group of responders (range, 3-13). A PSA decrease >50% was registered in 36% of the patients. Pain reduction was recorded in 44.4% of the patients and stability in 14.8%. RESULTS: The treatment was well tolerated and grade 3 toxicity was found in 2 cases of anemia and 2 cases of leukopenia without fever. CONCLUSIONS: The schedule is able to control the evolution of hormone-refractory prostate cancer and to give a clinical benefit. These results provide information for further clinical trials in a large series of elderly cancer patients.

Phase I-II parallel study of docetaxel on a bimonthly schedule in refractory metastatic breast carcinoma.

BACKGROUND: The 3-week schedule with docetaxel (DTC) 75-100 mg/2 is associated with severe neutropenia, gastro-intestinal side-effects and fluid retention in a significant proportion of patients, which may be of concern in more elderly or poor performance status patients. A phase I-II trial was carried out to test the feasibility and the activity of a new bimonthly schedule of DCT. PATIENTS AND METHODS: The trial included a phase I study which aimed at the identification of dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of DCT on a bimonthly schedule. The first group of three patients received DCT 40 mg/m2, and in absence of DLT, DCT dosage was escalated by 10 mg/m2/cycle until DLT was reached. In the phase II study, patients were randomized to receive: (a) standard 3-weekly DCT at the dose of 75 mg/m2 (calibration arm); or (b) bimonthly schedule with DCT at the dose recommended in the phase I study. All patients were pretreated with chemotherapy, mostly anthracycline-based regimens, for advanced/metastatic disease. Analysis of response rates, toxicity, and dose-intensity were the main aims of the study. RESULTS: The DLT was represented by severe myelosuppression which was recorded in all patients treated at 70 mg/m2 dose level. Therefore, the MTD was 60 mg/m2 on a bimonthly schedule. However, the dose recommended for the phase II trial was 50 mg/m2, because no difference in delivered dose-intesity was seen between the 50 and 60 mg/m2 dose levels, and the latter dosage was still associated with grade 3 neutropenia in most patients. The parallel phase II study showed that the bimonthly schedule of DCT (50 mg/m2) allows to deliver the same dose-intensity of DCT 75 mg/m2 every 3 weeks. Grade 3-4 side-effects were rather infrequent in patients treated with the bimonthly schedule. Overall response rate (ORR) was 41 and 44% for the DCT 50 mg/m2 bimonthly and the DCT 75 mg/m2 every 3 weeks, respectively. CONCLUSIONS: Data achieved in the phase I part of the study showed that DCT 50 mg/m2 every 15 days is the recommended dose for phase II studies, while results achieved in the phase II trial suggest that DCT 50 mg/m2 in a bimonthly schedule is active as second-line chemotherapy for MBC being able to induce an ORR in the range reported for DCT 75-100 mg/m2 every 3 weeks. The bimonthly schedule is, however, associated with relatively low toxicity. This characteristic may render the bimonthly schedule particularly attractive for future phase II trials of DCT in combination with other antineoplastic agents.

Pegylated liposomal doxorubicin with vinorelbine in metastatic breast carcinoma. A phase I-II clinical investigation.

A multicenter phase I-II trial was carried out with the aim of identifying the dose-limiting toxicity and the maximum tolerated dose of vinorelbine (VNR) in combination with pegylated liposomal doxorubicin at a dose of 20 mg/m(2) every 15 days in patients with metastatic breast carcinoma. In the phase I part of the trial, VNR was given at a dose of 20 mg/m(2) every 15 days to a group of 3 patients. In absence of unacceptable toxicity, VNR was escalated to 25, 30, and 35 mg/m(2) for subsequent groups of 3 patients, until the dose-limiting toxicity was reached. No case of palmar-plantar erythrodysesthesia was recorded in these patients. Grade 4 neutropenia, grade 3 thrombocytopenia, and grade 3 mucositis were the dose-limiting toxicities recorded in patients treated with VNR 35 mg/m(2). These side effects caused a substantial decrease in programmed dose intensity. Therefore 30 mg/m(2) was considered the maximum tolerated dose of VNR in combination with pegylated liposomal doxorubicin 20 mg/m(2), both given every 15 days. These dosages were employed for the treatment of further 18 patients included in phase II of the study. The overall response rate, calculated according to an intention to treat analysis, was 63% (95% CI: 44-80%), with 2 patients achieving a complete response. The median time to progression was 7.0 months or more (range 2-14 months). Median duration of objective responses was 8.4 months or more. The duration of the 2 complete responses was 9 and 14 months, respectively. Median duration of survival was 16.0 months or more (range from 4.0 to >or=24.0). Toxicity was generally mild and easily manageable. Neutropenia and mucositis were the most frequently recorded side effects. A case of palmar-plantar erythrodysesthesia was recorded in phase II of the study. In conclusion, the maximum tolerated dose of VNR in association with pegylated liposomal doxorubicin is 30 mg/m(2) on a bimonthly schedule. Moreover, the combination of VNR and pegylated liposomal doxorubicin is active against metastatic breast carcinoma and is associated with a good toxicity profile. Further studies with this combination regimen are warranted.

Vinorelbine and cisplatin for the treatment of recurrent and/or metastatic carcinoma of the uterine cervix.

BACKGROUND: To test the clinical activity and toxicity profile of the combination regimen of vinorelbine and cisplatin in a series of patients with carcinoma of the cervix uteri with de novo metastatic disease or recurrent disease after previous therapy. The main aims of the study included analysis of objective response rates, toxicity, and time to progression. PATIENTS AND METHODS: Forty-two eligible patients were enrolled into the trial and treated with cisplatin 80 mg/m(2) on day 1 and vinorelbine 25 mg/m(2) on day 1 and 8. This regimen was repeated every 21 days upon resolution of toxicity for 3 cycles before response assessment. Enrolled patients had a median age of 53 years, a median ECOG performance status of 1, and mostly a squamous cell histology (86%). Sixteen patients (38%) were treatment-naive since first diagnosed with widespread metastatic disease, 7% had only previous surgery, 31% radiotherapy, and 24% both radiation and surgical therapy. In previously radiated patients, 21% of patients had disease only within the radiation fields, 21% only outside the radiation fields, and 12% both inside and outside the radiotherapy portals. RESULTS: All patients were evaluable for response analysis. A complete response was achieved in 5 patients (12%), and a partial response in 15 cases (36%) for an overall response rate of 48% (95% CL 22-52%). Patients with recurrent disease within the previous radiation field (including those also with disease outside the radiation fields) showed a 28% overall response rate with no complete response, while patients with disease previously untreated with radiotherapy or with tumour deposits only outside of ratiation portals yielded a 57% overall response rate with a 18% complete response rate. Only 1 out of 8 patients with performance status 2 showed a major response (12%). Median time to progression was 5.6 months (range 2.0-14 months). The median overall survival of the whole series was 9.1 months. Hematological toxicity was the most frequent side-effect. Grade 3 vomiting was recorded in 9 patients (21%), and mild mucositis in 14% of patients. Grade 3 neutropenia was observed in 21% of patients, while grade 4 in 12% of cases with neutropenic fever was seen in 4 cases. Sixteen patients (38%) complained of grade 1-2 constipation, while grade 1-2 peripheral neuropathy was seen in 8 patients (19%). CONCLUSIONS: The results achieved in this trial suggest that the combination regimen of vinorelbine and cisplatin may be safely given to patients with metastatic and/or recurrent carcinoma of the uterine cervix. This regimen is active at least in terms of objective response rates. Although satisfactory results are still lacking, these results suggest that the vinorelbine-cisplatin regimen is worthy of further studies and may represent the basis for the development of new active regimens.