11 research outputs found
Phase I-II study of sequential combination of XELOX and bevacizumab plus erlotinib (XELOX-TARAV) in first line colorectal patients:Run in phase I part
Methods: Chemonaive mCRC patients were treated with OX, 130 mg/m2 day 1 plus
XEL, 1625 mg/m2/day days 1 to 14; B 7.5 mg/kg day 1; E, orally days 2 to 18 at 100 mg (I
dose level) and 150 mg (II level), every 3 weeks. Treatment was administered for
a maximum of 9 cycles or until PD or unacceptable toxicity (UT). The maximum
tolerated dose (MTD) was defined as the dose level immediately preceding that in
which dose-limiting toxicity (DLT) has been identified. DLT was the dose causing UT
(defined with conventional NCI criteria) in ‡2 patients within a 3-6 patients cohort
during the first cycle. Pharmacodynamic studies were conducted to evaluate tissue and
circulating biologic factors.
Results: To date 9 patients were enrolled. During the first cycle of therapy, according to
the phase I objective definition, DLT was recorded in 1 patient at dose level I (diarrhea
G3) and 2 patients at dose level II (diarrhea G3-4). Therefore, dose level II was defined
as the DLT and 3 additional patients were treated at I dose level and no further UT was
experienced. Overall, 43 complete cycles were administered (median 3; range 1-12).
Overall toxicity is reported in the following table.
Tumor shrinkage (5 pts) or stabilization (1 pt) were observed in 6/8 patients evaluable
for response assessment.
Conclusion: Diarrhea was responsible of DLT at II dose level (E 150 mg). E 100 mg is
the recommended dose to be combined with chemotherapy and B for the Phase II part
of the study. Pharmacodynamic correlative studies are ongoing
Oral antisense targeting protein kinase A type I causes antitumor and apoptotic effect in human cancer cells in vitro and in vivo and has cooperative activity in combination with antisense bcl-2.
Phase I-II study of xelox and bevacizumab plus erlotinib in sequential combination (XELO-TARAV) in first line colorectal cancer: Run in part.
PRECLINICAL AND PHASE I STUDY OF OXALIPLATIN AND TOPOTECAN IN COMBINATION IN HUMAN CANCER.
BACKGROUND:
DNA damage caused by platinum agents is frequently followed by induction of topoisomerase I, providing a rationale for use of platinum-based compounds with topoisomerase I inhibitors.
MATERIALS AND METHODS:
We studied the effect of a sequential schedule of oxaliplatin on day I and topotecan on days 2-5, in human colon and ovarian cancer cells in vitro, in nude mice bearing human cancer xenografts and finally in cancer patients in a phase I trial.
RESULTS:
We demonstrated a supra-additive effect of this combination on inhibition of colony formation and induction of apoptosis in vitro. We then demonstrated that the two agents in combination markedly inhibit tumor growth in nude mice. We translated these results into a clinical setting, conducting a phase I study in cancer patients with oxaliplatin 85 mg/m2 on day 1 and topotecan at doses escalating from 0.5 to 1.5 mg/m2 on days 2-5. Sixty cycles of treatment were administered to 18 patients affected prevalently by ovarian and colorectal cancer. Combination with topotecan 1.5 mg/m2 caused a dose-limiting toxicity. Therefore the maximum tolerated dose of topotecan was 1.25 mg/m2, at which six patients experienced a mild hematological and gastrointestinal toxicity. We also obtained evidence of clinical activity, particularly in ovarian cancer.
CONCLUSIONS:
Our results provide a solid biological and clinical rationale for a phase II trial at the recommended doses of oxaliplatin 85 mg/m2 and topotecan 1.25 mg/m2, possibly in ovarian cancer patients
mRNA PROFILING AS PREDICTIVE FACTOROF COMPLETE PATHOLOGICAL RESPONSE TO NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED RECTAL CANCER
Predictive factors of response to neoadjuvant chemoradiotherapy in rectal cancer patirnts.
Background: Pre-operative chemo-radiotherapy (CT-RT) produces a high rate of
response in rectal cancer patients (pts). Several evidences suggests that using 2 drugs
correlates with best responses and that complete pathologic response (cPR) induces
prolonged survival. The aim of the present analysis was the evaluation of the effect of
some biologic characteristics of the primary tumor on PR, as scored according to
Tumor Regression Grade (TRG) scale.
Methods: 45 pts, enrolled in a phase II trial, were treated with 2 cycles of CAP-OX
concomitantly with pelvic conformal radiotherapy (45 Gy). EGFR, p53, PARP,
XRCC, VEGFR and TS expression was determined by immunohistochemistry on
rectal biopsies obtained prior CT-RT initiation, and scored as percentage of
positive cells. The Spearman’s correlation test, t-test and logistic regression analysis
were used to explore the correlation between these biological factors and the TRG
(SPSS software). Biological factors expression was considered as a continuous
variable. TRG was both considered as 4 categories and coded as TRG1 (cPR) vs
TRG >=2.
Results: Among the 42 operated pts, cPR (TRG-1) was observed in 10 (23.8%); TRG-2
in 18 (42.9%); TRG-3 in 11 (26.2%); TRG-4 in 3 pts (7.1%). Paraffin embedded
biConclusions: A statistically significant inverse association was observed between TRG
and TS expression; a weak correlation was suggested between cPR and low EGFR,
VEGFR and PARP expression. Neither gender nor age significantly affected cPR.opsies from primary tumor were available for all pts
Mitoxantrone, etoposide and bleomycin (MEB) chemotherapy in non-Hodgkin's Lymphoma patients non-elegible for standard cyclophosphamide, doxorubicin vincristine and prednisone (CHOP) combination.
A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FLFOX-4) as first-line treatment of advanced gastric cancer patients.
Background: The purpose of this study was to assess the toxicity and clinical
activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil and
folinic acid administered every 2 weeks (FOLFOX4 regimen) in patients with
advanced gastric cancer (AGC).
Patients and methods: Sixty-one previously untreated AGC patients were treated
with oxaliplatin 85mg/m2 on day 1, folinic acid (FA) 200mg/m2 as a 2-h infusion
followed by bolus 5-fluorouracil (5-FU), 400 mg/m2 and a 22-h infusion of 5-FU,
600 mg/m2, repeated for two consecutive days every 2 weeks.
Results: All patients were assessable for toxicity and response to treatment. Patient
characteristic were: sex (male, 38; female, 23); median age, 64 years (range, 47–75
years); Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0,
nine patients; 1, 39 patients; 2, 13 patients; metastatic disease, 56 patients; locally
advanced disease, five patients. Four (7%) complete responses (CR) and 19 partial
responses (PR) were observed (overall response rate, 38%). Stable disease (SD) was
observed in 22 (36%) patients, with progressive disease (PD) in the other six (10%)
patients. Median time to progression (TTP) and median overall survival (OS) were
7.1 and 11.2 months, respectively. NCI common toxicity criteria grade 3 and 4
hematologic toxic effects were neutropenia, anemia and thrombocytopenia in 36%,
10% and 5% patients, respectively. Grade 3 peripheral neuropathy was recorded in
three (5%) patients. No treatment-related deaths were observed.
Conclusion: FOLFOX-4 is an active and well tolerated chemotherapy. RR, TTP and
OS were comparable with those of other oxaliplatin-based regimens, suggesting a
role for this combination in gastric cancer
Manuale di Oncologia Clinica
Manuale di Oncologia Clinica rivolto agli studenti delle Facolt\ue0 di Medicina e Chirurgia e agli specializzandi in Oncologia Medic