Brain metastases in patients with non-small cell lung cancer: focus on the role of chemotherapy.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
V Adamo
Publications and source records attributed to V Adamo.
Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.
BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression.
Adult↗
Novel P53 mutations detected by FAMA in colorectal cancers.
BACKGROUND: The aim of the study was to identify p53 gene mutations by FAMA (fluorescence-assisted mismatch analysis) in colorectal cancers. PATIENTS AND METHODS: Analytical scanning of the p53 gene (exons 5-9) was performed in colon cancer samples from 44 consecutive patients by FAMA. FAMA is a semiautomatic scanning approach based on the chemical cleavage of the mismatch in fluorescently labeled heteroduplex DNA, obtained from the combination of a normal and a mutated allele. FAMA has already shown optimal levels of diagnostic accuracy and sensitivity in detecting gene mutations (nucleotide substitutions, insertions/deletions) both at the germline and somatic level. The peculiar feature of FAMA is its ability to detect and localize mutations, by a redundant pattern of signals due to fluorescent DNA fragments generated by chemical cleavage. Moreover, previous data have demonstrated that normal contaminating DNA from stromal cells in the sample does not affect the sensitivity of the procedure, leading to the identification of the mutation even when the ratio mutant/normal allele is 10%. RESULTS: Eighteen mutations (12 missense, one nonsense, two deletions, three nucleotide substitutions at the level of the splice-junctions) and two polymorphisms were detected by FAMA in 17 patients (39%) and then confirmed by automated sequence analysis. Six of 18 mutations (33%) were not previously reported for colon cancer samples and two of 18 lesions (11%) were identified as novel p53 mutations. CONCLUSIONS: Analytical scanning of the p53 gene by FAMA in DNA from colon cancer samples provides a sensitive, accurate and specific diagnostic procedure for routine clinical application.
Colorectal Neoplasms↗
Molecular detection of TP53, Ki-Ras and p16INK4A promoter methylation in plasma of patients with colorectal cancer and its association with prognosis. Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.
BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques.
Aged↗
Significance of P16INK4A hypermethylation gene in primary head/neck and colorectal tumors: it is a specific tissue event? Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.
BACKGROUND: Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. PATIENTS AND METHODS: The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of 33 SG tumor patients and in a consecutive series of 66 sporadic CRC patients. RESULTS: Hypermethylation was observed in 9% of the LSCC cases, in all cases of SG cancer and in 21% of the CRC cases. No significant association was observed between p16 hypermethylation and clinicopathological variables in all the tissue samples analyzed. Moreover at univariate analysis p16 mutations were not independently related at disease relapse and death in LSCC and CRC. CONCLUSIONS: The results of this study suggest that the lack of p16 function could happen in advanced stage of SG tumors.
Carcinoma, Squamous Cell↗
Phase II study of gemcitabine and cisplatin in patients with advanced or metastatic bladder cancer: long-term follow-up of a 3-week regimen.
BACKGROUND: Bladder cancer is the fifth most common cancer among men and the seventh among women. At diagnosis, at least 25% of bladder cancer tumors are locally or systemically advanced. Systemic chemotherapy is the only current modality for advanced or metastatic transitional cell carcinoma of the bladder. Recently, a phase III randomized study has demonstrated that the regimen with gemcitabine (GMC) and cisplatin (CDDP) had a survival advantage similar to the standard M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin), with a better safety profile. AIM: It was the aim of this study to evaluate the tumor response rate, the median time to progression, the median survival and toxicity in a 21-day schedule with GMC and CDDP in patients with advanced/metastatic bladder cancer. PATIENTS AND METHODS: From September 1998 to December 2000, 27 patients with advanced/metastatic transitional cell carcinoma were enrolled. All patients received 1,200 mg/m(2) GMC administered as a 30-min intravenous infusion on days 1 and 8, and 75 mg/m(2) CDDP as a 1-hour infusion on day 2. Cycles were repeated every 21 days. The patients had a median age of 59.8 years (range 39-75) and an Eastern Cooperative Oncology Group performance status of 0-2. RESULTS: Twenty-five patients were valuable for toxic effects, length of survival and tumor response. The statistical analysis was performed in May 2004. Mean and median follow-up were 20.23 and 13.2 months (range 2-68), respectively. The overall remission rate (complete response + partial response) was 48% (95% CI 28.4-67.6%). The median time to progression was 9 months (range 2-56). The median duration of survival for all patients was 13.2 months (range 2-68+), with 1-year and 23-month survival rates of 60 and 20%, respectively. There was no grade 4 toxicity or treatment-related death. Grade 3 anemia was observed in 4 patients (16%) and grade 3 thrombocytopenia occurred in 6 patients (24%). No grade 3-4 nausea/vomiting or neutropenia was observed. CONCLUSION: GMC and CDDP is an active schedule with a good safety profile in a 21-day regimen. It may be a valid alternative to the standard 28-day regimen due to its high tumor response and survival with a low incidence of toxicity, especially in pretreated and metastatic patients.
Adult↗
Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study.
The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73-1.09) for patients receiving FA and 0.99 (95% CI 0.80-1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80-1.30) and 0.94 (95% CI 0.73-1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients.
Adult↗
Cabergoline: a safe, easy, cheap, and effective drug for prevention/treatment of ovarian hyperstimulation syndrome?
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Cabergoline↗
A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer.
The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.
Adult↗
Prevalence and management of pain in Italian patients with advanced non-small-cell lung cancer.
Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3% very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i). pain self-assessment should be part of oncological clinical practice; (ii). pain control should be a primary goal in clinical practice and in clinical trials; (iii). physicians should receive more training in pain management; (iv). analgesic treatment deserves greater attention in protocols of anticancer treatment.
Adult↗
Induction chemotherapy to weekly paclitaxel concurrent with curative radiotherapy in stage IV (M0) unresectable head and neck squamous cell carcinoma: a dose escalation study.
The purpose was to determine the maximum tolerated dose (MTD) of weekly paclitaxel with concurrent, daily irradiation in patients with unresectable head and neck squamous cell carcinoma previously submitted to induction chemotherapy. Patients with stage IV, and unresectable tumor and/or node/s were enrolled. Nine male patients were submitted to a course of paclitaxel 175 mg/m2 day 1 and cisplatin 75 mg/m2 day 2 given every 3 weeks for three courses. Curative radiotherapy (RT) started 3 weeks after the last cycle of chemotherapy with the goal of delivering a total dose of 66-70 Gy. During RT weekly paclitaxel was administered for 6 courses if feasible; paclitaxel was given according to a dose escalation schema in cohorts of three patients. Dose level A, 30 mg/m2; dose level B, 40 mg/m2; dose level C, 50 mg/m2. During weekly paclitaxel the major toxicity was mucositis that required a treatment break in two of three patients in dose level C; mucositis grade 4 required interruption of paclitaxel administration in all these patients. RT can be given in a continuous fashion with weekly paclitaxel after induction chemotherapy. The MTD of weekly paclitaxel was 40 mg/m2.
Aged↗
Venous damage prevention by defibrotide in vinorelbine-treated patients.
GOALS: The aim of our study was to evaluate the incidence of venous toxicity induced by vinorelbine administration in patients who received a preventive therapy with defibrotide. PATIENTS AND METHODS: From July 1996 to July 2002 we treated 203 patients with vinorelbine, 51 with vinorelbine alone and 152 with vinorelbine in combination with other drugs via peripheral vein infusion. Of the 203 patients, 123 were male and 80 female with a median age of 67 years (range 18 to 82 years), and 118 were chemotherapy-naive. Defibrotide was delivered i.v. at a dose of 400 mg in 250 ml normal saline. After infusion of 125 ml over about 15 min, vinorelbine mixed with 10 ml normal saline was delivered as quick brief repeated pulses over 5 min through the plastic tube, followed by infusion of the remaining defibrotide. The specific Rittenberg scale was used to assess venous irritation episodes. RESULTS: Among a total of 1336 vinorelbine infusions, with a median of five infusions per patient, the incidence of venous irritation episodes graded according to Rittenberg scale was 1.1% (15), of which 0.6% (8) were grade 2 and 0.5% (7) grade 1. Globally, 15 patients (7.3%) developed venous toxicity after a median of 3 infusions (range 1-14), but no patient had more than one event. CONCLUSION: Our findings support the use of defibrotide as an effective, safe and low-cost means for preventing vinorelbine-related venous damage.
Adult↗
Preliminary evidence on the safety of ICSI with testicular spermatozoa in HCV-infected male: a case report.
An infertile couple with a hepatitis C (HCV) RNA-positive male came to our attention. We were not able to perform an assisted reproduction technology (ART) procedure with ejaculated spermatozoa free of HCV RNA using gradient centrifugation and swim up, due to retrograde ejaculation and severe male factor. ICSI with testicular spermatozoa was the most rational therapeutic approach. The couple was informed about the lack of adequate data on the safety of this therapeutic approach. The risks of this procedure were accepted by the couple. Testicular sperm aspiration combined with ICSI (TESA-ICSI) was performed. After a negative result for an HCV RNA PCR on the embryos' culture medium, four embryos were transferred to the uterine cavity on the third day. The procedure resulted in an ongoing clinical pregnancy, and HCV antibody determinations performed in the mother at the 12th and 24th week of pregnancy were negative. The pregnancy ended at the 39th week due to endo-uterine death. No malformation or hepatic pathologies were found in the conceptus. A second TESA-ICSI cycle is ongoing. This preliminary evidence suggests that, in HCV sero-positive males, ICSI with testicular spermatozoa may be a safe procedure. However, we need more observations to clarify if ART is really able to reduce horizontal and vertical transmission of HCV in sero-discordant couples (only the male infected) in comparison with natural conception.
Female↗
Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer.
PURPOSE: To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin (reference regimen) in response rate for patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to receive gemcitabine 1,250 mg/m(2) days 1 and 8 plus cisplatin 75 mg/m(2) day 2 every 21 days (GC arm), or paclitaxel 225 mg/m(2) (3-hour infusion) then carboplatin (area under the concentration-time curve of 6 mg/mL x min), both on day 1 every 21 days (PCb arm), or vinorelbine 25 mg/m(2)/wk for 12 weeks then every other week plus cisplatin 100 mg/m(2) day 1 every 28 days (VC arm). RESULTS: Six hundred twelve patients were randomized to treatment (205 GC, 204 PCb, and 203 VC). Overall response rates for the GC (30%) and PCb (32%) arms were not significantly different from that of the VC arm (30%). There were no differences in overall survival, time to disease progression, or time to treatment failure. Median survival for the GC, PCb, and VC groups was 9.8, 9.9, and 9.5 months, respectively. Neutropenia was significantly higher on the VC arm (GC 17% or PCb 35% v VC 43% of cycles, P <.001), as was thrombocytopenia on the GC arm (GC 16% v VC 0.1% of cycles, P <.001). Alopecia and peripheral neurotoxicity were most common on the PCb arm, as was nausea/vomiting on the VC arm (P <.05). CONCLUSION: Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.
Adult↗
Ipsilateral supraclavicular lymph nodes metastases from breast cancer as only site of disseminated disease. Chemotherapy alone vs. induction chemotherapy to radical radiation therapy.
BACKGROUND: To define the role of radiotherapy (RT) in the treatment of ipsilateral supraclavicular lymph-nodes metastases (ISLM) from breast cancer as only site of disseminated disease, we started a prospective non-randomized clinical trial in 1989. Here we report the final results with a median follow-up of 8.75 years. PATIENTS AND METHODS: Thirty-seven patients (pts), with ISLM from breast cancer, were consecutively enrolled into two arms. Arm A (18 pts): chemotherapy (CT) for six courses. Arm B (19 pts): CT for three courses followed by RT to the site of ISLM at 'radical' dose of 50-60 Gy. RESULTS: In arm A, a median Time to Progression (TtP) of 7 months with a median Overall Survival (OS) of 28 months was recorded. In comparison, patients in arm B had a longer median TtP with 20 months as well as a better median OS with 41 months, respectively. An actuarial five-year disease-free survival of 5.5% was obtained in arm A vs. 21% in arm B. A statistically significant difference in TtP was demonstrated between the two groups (P = 0.01). CONCLUSIONS: These data demonstrate that a better event-free survival could be achieved in patients with ISLM submitted to induction CT and radical irradiation. This also translated into a longer survival although this did not achieve statistical significance. We want to stress the importance of local control by RT since it does imply that not all of these patients have micrometastases at the time of relapse in the supraclavicular fossa.
Adult↗
Etoposide, l-leucovorin and fluorouracil (ELF) regimen in metastatic gastric cancer: a phase II study.
The role of chemotherapy in metastatic gastric cancer (MGC) is predominantly palliative, therefore regimens with mild toxicity and acceptable activity should be preferred. The combination of etoposide, leucovorin and 5-fluorouracil (ELF) is suitable chemotherapy in this situation. We have enrolled 33 patients with MGC, using the following chemotherapy schedule: l-leucovorin 150 mg/m2 10 minute i.v., followed by etoposide 120 mg/m2 50 minute i.v., followed by 5-fluorouracil 500 mg/m2 10 minute i.v. on days 1-3, every 22 days. All patients are valuable for response, toxicity and survival. Two patients achieved complete response (6%), 10 patients (30%) had a partial response (PR), 9 patients (27%) had stabilization of disease (SD) and 12 patients had disease progression (PD). The median survival for all patients was 6 months (range, 1 to 40+). ELF was well tolerated, the main toxicity being myelosuppression. No toxic deaths occurred. In conclusion, the ELF regimen in our trial demonstrated, in this kind of patient, moderate activity in the absence of relevant toxicity, confirming its suitability in patients in generally poor condition.
Adult↗
Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project.
PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non-small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 100 mg/m(2) on day 2, every 28 days, or mitomycin 6 mg/m(2), ifosfamide 3,000 mg/m(2), and mesna on day 1 plus cisplatin 100 mg/m(2) on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P =.029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P =.877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P <.001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P <. 001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.
Adult↗
Intralesional sonographically guided injections of lymphokine-activated killer cells and recombinant interleukin-2 for the treatment of liver tumors: a pilot study.
Primary and metastatic liver cancers have a poor prognosis. At present, sonographically guided alcohol injection results in a partial reduction of cancer masses even if severe toxic effects (including pain and bleeding) are always present. For these reasons, a pilot study was started to evaluate the feasibility of an intralesional adoptive immunotherapeutic approach, using lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2). Nine patients (one with primary hepatocarcinoma and eight with liver metastases) entered the study. Four cycles of weekly injections of LAK cells (ranging from 2 to 9 x 10(8)) and 10(6) IU rIL-2 were performed percutaneously under ultrasonic guidance. In the same period, 3 x 10(6) IU rIL-2/day, for 24 days, was injected subcutaneously. All patients but one completed the therapy. Side effects were limited to grade 1-2 fever and were mostly related to rIL-2 subcutaneous injections. No patients complained of having pain during intralesional therapy. Two complete responses were detected. One partial response, four stable diseases, and one progressive disease were observed. One patient was not evaluable. These preliminary results suggest that sonographically guided intralesional adoptive immunotherapy of liver tumors is feasible, safe, and could offer promising therapeutic advantages in cancers for which conventional treatment is generally unsatisfactory.
Adult↗