[Show abstract][Hide abstract] ABSTRACT: Goals: M is a non-pegylated liposomal doxorubicin exhibiting
reduced cardiotoxicity as compared to doxorubicin. Combination
of M and C has demonstrated efficacy in first line treatment of
metastatic BC, however fewdata are available in neoadjuvant setting,
especially in combination with T. The aims of the studywere activity,
in terms of pathological complete response (pCR; ie, no remaining
invasive tumor in breast and lymphnodes) and safety of a sequential
schedule of M and C +/− T followed by weekly P +/− T.
Methods: Estrogen receptor (ER), progesterone receptor (PgR),
HER2+ (defined as 3+ overexpression by immunoistochemical testing
or HER2 amplification by fluorescent in situ hybridisation) and
Ki67 index were assessed in core needle biopsies at baseline and
in residual tumour after chemotherapy. Patients with stage II/III
BC received 4 cycles of MC (myocet 60mg/m2, cyclophosphamide
600mg/m2 on day 1 every 3 weeks), followed by 12 weekly doses
of P (paclitaxel 80mg/m2); all patients with HER2+ disease received
T in combination with chemotherapy (trastuzumab loading dose of
8 mg/kg followed by 3 cycles of 6 mg/kg alongside MC; 2 mg/kg per
week with the following 12 P administrations).
Results: 68 patients were enrolled, median age 55 years (range
34–72). Tumour characteristics were: stage IIA 11 patients, IIB 16,
IIIA 22, IIIB 18 (5 inflammatory BC), IIIC 1; ER+ and PgR+/−
36 patients, triple negative 12, HER2+ 20 (ER+ and/or PgR+ 11);
Ki67 ≤15% in 12 (17.6%). To date, 58 patients were evaluable for
pathological response: pCR was obtained in 16 (27.6%). The rate of
pCR in HER2+ and HER2− BC was 63.1% (12/19) and 10.2% (4/39),
respectively. Clinical response was evaluable in 62: CR in 28 (45.2%)
and PR in 24 (38.7%). Conservative surgery was performed in 20 out
of 61 patients (32.8%). The most frequently observed grade 3–4 AEs
were: grade 3 neutropenia 5 patients (8.1%), grade 3 paresthesia
3 (4.8%), grade 3 vomiting 3 (4.8%). Only 1 patient experienced an
asymptomatic decrease of ejection fraction lower than 50%.
Conclusion: The use of M in this sequential regimen resulted to
be active, despite of the high rate of patients with ER+ disease and
with locally advanced cancer. Consistently with previous data, pCR
was higher in patients with HER2+ BC.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Elderly patients are generally underrepresented in the study populations of combination chemotherapy trials. This study evaluates the efficacy and safety of a modified FOLFOX regimen in elderly patients with metastatic gastric cancer and presenting associated disease(s). METHODS: A total of 43 patients aged ≥70 years received oxaliplatin 85 mg/m(2) together with 6S-leucovorin 200 mg/m(2) on day 1, followed by a 46-h infusion of 5-fluorouracil 2,400 mg/m(2), every 2 weeks. Assessment of response was performed every four cycles according to RECIST criteria. RESULTS: Median patient age was 74 years (range, 70-83 years). Overall response rate was 34.9 % [95 % confidence interval (CI), 20.6-49.1, with 3 complete responses and 12 partial responses. Grade 3 neutropenia occurred in 4 patients (9.3 %), fatigue in 3 patients (7.0 %), and vomiting in 2 patients (4.6 %). Grade 2 and 3 peripheral neuropathy was observed in 5 patients (11.6 %) and 1 patient (2.3 %), respectively. No treatment-related death was observed. Median progression-free and overall survival were 6.8 and 10.5 months, respectively. CONCLUSIONS: This modified FOLFOX regimen is an active and well-tolerated treatment for elderly patients with metastatic gastric cancer and also represents a good therapeutic option in patients with associated disease(s).
Gastric Cancer 10/2012; 16(3). DOI:10.1007/s10120-012-0204-z · 3.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this case report we describe the case of a patient with multiple bone metastases of NSCLC, adenocarcinoma with exon 21 point-mutation of EGFR, treated with gefitinib. After only 3 months, FDG-PET/CT scan showed a complete response of bone metastases and right hylar adenopathy. Implications for need of early use of FDG-PET/CT scan after gefitinib treatment are discussed
[Show abstract][Hide abstract] ABSTRACT: The combination of docetaxel, cisplatin, and 5-fluorouracil (5-FU) has demonstrated a survival advantage over cisplatin and 5-FU, but with substantial hematological toxicity. We aimed to evaluate the efficacy and toxicity of a sequential regimen with cisplatin, leucovorin, and 5-FU (PLF) followed by docetaxel in metastatic gastric cancer patients.
Treatment consisted of 4 cycles of biweekly PLF (cisplatin 50 mg/m(2) as a 30-min infusion on day 1, leucovorin 200 mg/m(2) in a 2-h infusion, and 5-FU 2,800 mg/m(2) in a 48-h continuous infusion starting on day 1) followed, in cases of response or stable disease, by 3 cycles of docetaxel (75 mg/m(2), every 3 weeks).
Thirty-four patients were enrolled, with an average age of 64 years (range 34-69). The main cumulative grade 3-4 toxicities were: neutropenia (38.2%), febrile neutropenia (11.8%), and fatigue (14.7%). After the planned 7 cycles of treatment, the overall response rate was 38.2% (95% confidence interval [CI] 21.9-54.6), with 3 complete and 10 partial responses. Median progression-free survival and overall survival were 4.8 and 10.6 months, respectively.
For patients with metastatic gastric cancer, the sequential administration of cisplatin, leucovorin, 5-FU, and docetaxel may be an effective palliative option and offers a far more favorable toxicity profile than the simultaneous use of docetaxel, cisplatin, and 5-FU.
Gastric Cancer 01/2012; 15(4):419-26. DOI:10.1007/s10120-011-0134-1 · 3.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Efficacy of this drug was documented in the BR.21 trial showing that adenocarcinoma, female gender, Asian ethnicity and never-smoker status are predictive of clinical response to erlotinib. Retrospective studies documented the same benefits for elderly patients as young patients in terms of response, progression-free survival, and overall survival. The primary aim of our trial was to confirm these findings in a prospective way; the secondary aim was to identify if the aforementioned clinical characteristics may be predictive of response even in elderly patients. The trial included 31 patients with pretreated stage IIIB (2) and IV (29) non-small cell lung cancer (NSCLC). Median age was 75 years (range: 65-85). Twenty-seven patients were current/former-smokers and four never-smokers. Twenty-three patients are evaluable for response. Objective response rates were reported in five patients (16%). Five patients had stable disease (16%) and 13 progressive disease (43%). Seven patients had a "clinical benefit" from erlotinib (22.5%; 95% C.I.: 7.9-37.2%). Grade 3 skin rash was recorded in three patients (10%). Median survival was 9 months (range 1-30). Median time to progression was 3 months (range: 1-24 months). Our study confirmed erlotinib activity and safety as second- and third-line treatment in elderly patients with advanced NSCLC, especially in terms of median survival. Even though this trial does not allow us to draw a definitive conclusion about the role of a particular clinical characteristic predictive of response, the "clinical benefit" was documented especially in females, in patients with adenocarcinoma histology and skin rash, confirming previous retrospective data.
[Show abstract][Hide abstract] ABSTRACT: Visceral metastases of breast cancer have been commonly treated with "aggressive" anthracyclines/taxanes-based chemotherapy. In contrast, this case report concerns an elderly patient with advanced breast cancer (pleural effusion, peritoneal carcinosis, and bone metastases) who firmly declined intravenous chemotherapy and was treated for a long time (28 months) with oral vinorelbine. The oral formulation of this drug had activity and a high safety profile, enabling the patient's wishes to be respected.
Breast Cancer 09/2009; 19(3):275-7. DOI:10.1007/s12282-009-0156-2 · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Paclitaxel and platinum-based chemotherapy is considered to be a standard approach for locally advanced and metastatic non-small-cell lung cancer (NSCLC). In recent years, weekly paclitaxel has been widely used for its safety profile, especially in breast and ovarian cancer. Otherwise, only a few studies are available in NSCLC. The aim of our study was to investigate the activity and safety of weekly paclitaxel in elderly patients with locally advanced (stage IIIB) and metastatic (stage IV) NSCLC.
Twenty-seven patients entered the study; 10 had stage IIIB disease (5 "wet" and 5 "dry"), and 17 had stage IV disease. Median age was 73 years (range, 70-83 years). Sixteen patients (59%) presented with comorbidities. The schedule was weekly paclitaxel 80 mg/m2 for 6 weeks with 2 weeks of rest (1 cycle).
All patients were evaluable for response and toxicity; a median of 1 cycle was administered (range, 1-5 cycles). Partial responses were recorded in 9 patients (37.5%; 33.3%, according to intention-to- treat analysis; 95% CI, 15.5%-51.1%); 7 had stable disease (29%), and 8 had progressive disease (33.5%). Median time to progression was 5 months (range, 1-23 months), and median survival was 12 months (range, 1-36 months). Grade 2/3 asthenia was the main toxicity in 7 patients (29%); a hypersensitivity reaction presented in 1 patient. No other episode of grade 3/4 toxicity was recorded.
Our study confirmed that paclitaxel 80 mg/m2 weekly is active in patients with locally advanced and metastatic NSCLC with a good safety profile; this schedule might be considered an alternative choice to gemcitabine or vinorelbine as first-line treatment in elderly patients, particularly patients with comorbidities. Phase III studies that compare these third-generation drugs are warranted to draw definitive conclusion about the best approach in these patients.
Clinical Lung Cancer 10/2008; 9(5):280-4. DOI:10.3816/CLC.2008.n.043 · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the activity and safety of a schedule with a low dose of pegylated liposomal doxorubicin (PLD) and weekly paclitaxel in operable and locally advanced breast cancer patients. Thirty-five patients with histologically confirmed, operable, and locally advanced breast cancer entered the study. The median age was 59 years (range 31-74 years). The schedule was biweekly PLD at the dose of 15 mg/m for four administrations and weekly paclitaxel at the dose of 80 mg/m for eight administrations. All patients were evaluable for response and toxicity. Twenty-six patients responded (74%): three (8%) had a complete response and 23 (66%) had a partial response, seven (23%) remained stable, and one experienced progression (3%). Fifteen of 27 operable patients (55%) underwent conservative surgery. Three patients (9%) had a pathological complete response and the disappearance of infiltrating disease was documented in three other patients. The main toxicity was hand-foot syndrome (grade 3 in four patients; 11%). Other nonhematological grade 3 toxicities included stomatitis in three patients (8%) and liver toxicity in one patient (3%). Grade 3-4 neutropenia was documented in another three patients and dose reduction was necessary in two patients. The fourth administration of PLD was suspended in four patients for grade 2-3 hand-foot syndrome. No symptoms were related to impairment of cardiac function and no death related to toxicity occurred. The combination of biweekly PLD and weekly paclitaxel was active in operable and locally advanced breast cancer with a manageable safety profile.
[Show abstract][Hide abstract] ABSTRACT: Capecitabine is an orally administered precursor of 5'-deoxy-5-fluorouridine that was rationally designed to generate 5-fluorouracil (5-FU) preferentially in tumor tissue. The drug enables chronic dosing that mimics continuous infusion of 5-FU. Phase II trials of capecitabine at 1250 mg/m2 twice daily for 14 days followed by 7 days of rest, is active in anthracycline- and taxane-pretreated patients; the main toxicity is palmar-plantar erythrodysesthesia, diarrhea, and nausea. To overcome these side effects, the dose has been reduced to 1000 mg/m2 twice daily with a better therapeutic profile and encouraging efficacy. The aim of our study was to confirm safety and activity of capecitabine at lower doses in patients with metastatic breast cancer (MBC).
Thirty-seven patients with advanced breast cancer entered the study. The first 7 patients were treated with capecitabine 1250 mg/m2 twice daily (for 14 days followed by 7 days of rest) and the next 30 patients with capecitabine 1000 mg/m2. The median age was 62 years (range, 38-87 years). Thirteen patients were chemotherapy naive and 24 were pretreated with chemotherapy (9 patients, 1 line; 15 patients, > or = 2 lines). Anthracyclines and/or taxane schedules were administered in 22 patients. Soft tissue metastases were documented in 36 patients; visceral metastases in 24 patients; visceral and soft tissue metastases in 23 patients.
Thirty patients were evaluable for response (5 at "higher" dose and 25 at "lower" dose) and all for toxicity. Overall objective response rate was 57% (5 complete responses and 12 partial responses); 95% CI, 39%-74%; stable disease 20% and progressive disease 23%. Eight of 13 chemotherapy-naive patients (61.5%) and 9 of 24 pretreated patients (37.5%) responded to capecitabine, according to the intent-to-treat principle (6 of 9 responses were obtained at a lower dose). Three responses at the "higher" dose and 14 at the "lower" dose were reported. Median time to progression was 7 months (range, 1-38 months) and median overall survival was 19 months (range, 2-47 months). Toxicity was as follows: grade 2/3 palmar-plantar erythrodysesthesia in 9 patients (24%), grade 2/3 asthenia in 7 patients (19%), grade 2 vomiting in 4 patients (11%), grade 2 renal toxicity in 1 patient, grade 2 skin reaction in 1 patient, and suspected cardiac toxicity in 1 patient.
Our study confirmed that a lower dose of capecitabine has a good toxicity profile and is active in patients with MBC.
Clinical Breast Cancer 12/2007; 7(11):857-60. DOI:10.3816/CBC.2007.n.050 · 2.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intravenous vinorelbine has demonstrated its efficacy and tolerability in advanced non-small-cell lung cancer (NSCLC). An oral formulation of vinorelbine has been developed, and a number of phase II studies have shown its activity in chemotherapy-naive NSCLC, even in elderly patients, but no study has been performed to test activity and toxicity of oral vinorelbine in pretreated patients. The aims of our study were to investigate the activity and toxicity of oral vinorelbine in patients with NSCLC as salvage treatment.
Twenty pretreated patients with locally advanced (n = 6) and metastatic (n = 14) NSCLC entered the study. The schedule was oral vinorelbine 60 mg/m(2) once a week until progression or development of unacceptable toxicity. Median age was 70 years (range, 49-84 years).
Seventeen patients were evaluable for response and all for toxicity. A median of 9 cycles were administered (range, 2-21 cycles). No objective responses were reported, 5 patients experienced stable disease, and 12 patients had progressive disease. Median time to progression was 2 months (range, 1-6 months), and median survival was 4 months (range, 1-13 months). Treatment was well tolerated, with grade 4 neutropenia in 1 patient (heavily pretreated); grade 2 diarrhea in 2 patients; asthenia in 2 patients; and abdominal pain in 1 patient.
Oral vinorelbine 60 mg/m(2) once a week is a very safe schedule in heavily pretreated locally advanced and metastatic NSCLC; however, at this dose, the drug is inactive. Other phase II studies with oral vinorelbine 80 mg/m(2) weekly are warranted.
Clinical Lung Cancer 06/2007; 8(6):382-5. DOI:10.3816/CLC.2007.n.019 · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This case report concerns an elderly patient with liver and bone metastases of breast cancer successfully treated for two-years with capecitabine as first line chemotherapy without any side effect.
[Show abstract][Hide abstract] ABSTRACT: In an open prospective study. 40 patients with progressing painful bone metastases received 45 mg pamidronate by 1-h infusion every 3 weeks. A total of 27 patients (67%; 95% CI 53%-81%) experienced relief of pain as shown by the significant reduction of the bone pain score after three pamidronate administrations (from 2.25 +/- 0.64 to 1.15 +/- 0.36). Furthermore, 20 patients (60%) reduced their consumption of analgesics. We did not observe any objective response by skeletal radiological examination. In 11 patients presenting a skeletal progressive disease, bone pain improved, as well as their mobility score, but not their fatigue score. Treatment was well tolerated. Only 1 patient discontinued the treatment because of fever and cutaneous rash after the first administration. In conclusion, our results seem to confirm that pamidronate exerts a benefical effect on bone pain and mobility impairment in patients with painful osteolytic bone metastases.
Supportive Care Cancer 02/1996; 4(1):31-3. DOI:10.1007/BF01769872 · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A total of 26 patients with advanced colorectal cancer received 60 mg/m2 methotrexate i. v. on days 1 – 4; 400 mg/m2 5-fluorouracil i. v. on days 2, 3, 5, and 6; and 100 mg/m2 6S-leucovorin i. v. on days 2, 3, 5, and 6. Interferon-α2b at a dose of 3 million U was given i. m. daily for the 6 days
of chemotherapy. Courses were repeated every 3 weeks. There were four partial responses for a response rate of 15% (95% confidence
interval 2 – 28%). In all, 14 patients expressed grade 3 toxicity; 9 patients had diarrhea, 3 had stomatitis, and 2 developed
leukopenia. In conclusion, multimodal biochemical modulation of 5-fluorouracil, at least on this schedule, does not seem to
be effective, as it results in severe toxicity.
Cancer Chemotherapy and Pharmacology 01/1996; 38(4):385-386. DOI:10.1007/s002800050499 · 2.77 Impact Factor