pattyz
06-20-2006, 08:27 AM
Thought I would post (re-post?) this information, as the topic comes up fairly frequently. I can attest to the good response (for me) using Xeloda/Temodar for brain mets/bc primary. This small study came to my attention AFTER I began my tx protocal with these drugs.
SABCS ABSTRACT:
[San Antonio Breast Cancer Symposium]
[1079] Phase I study of capecitabine (C) in combination with temozolomide (T) in the treatment of patients with brain metastases from breast carcinoma.
Rivera E, Valero V, Francis D, Brewster A, Royce M, Esteva F, Murray JL, Pusztai L, Hortobagyi GN.. The University of Texas M.D. Anderson Cancer Center, Houston, TX
Background: T is an oral alkylating agent that is
currently being used for the treatment of primary
brain tumors due to its ability to cross the
blood-brain barrier. C has been approved for use in
the treatment of metastatic breast cancer patients who
have failed anthracyclines and taxanes. It is well
known that C crosses the blood-brain barrier and has
activity in the brain. Options are limited for
patients with brain metastases.
Materials and Methods: We evaluated the activity of
both drugs in combination for the treatment of brain
metastases not amenable to surgery. Patients were
allowed in the study if they had new onset brain
metastases from breast cancer, had declined radiation
therapy, and were neurologically stable. They were
also eligible if they had evidence of recurrence or
progression of brain metastases after whole brain or
stereotactic radiation therapy. C was started at 1800
mg/m2 in 2 divided doses. T was given at a starting
dose of 75 mg/m2 in one daily dose. Each drug was
given concomitantly every day for 5 days (day 1-5)
followed by 2 days of rest and restarted again for an
additional 5 days (days 8-12). Each cycle was repeated
every 21 days. We have enrolled a total of 16 pts — 6
pts at dose level 0 (C/T — 1800/75), 6 pts at dose
level 1 (C/T — 1800/100), and 4 pts at dose level 2
(C/T — 2000/100).
Results: Five pts had recurrent brain metastases and
had been previously treated with radiation therapy.
The median age is 51 yrs (range, 32-77). All pts had a
Zubrod performance status < 1. Ten pts were ER and/or
PR positive. No grade 4 toxicities have been reported.
Grade 3 toxicity includes headaches (2 pts), vomiting
(1 pt), constipation (2 pts), fatigue (2 pts),
nonneutropenic fever (1 pt). We have observed 1 CR, 1
PR, 6 MR, and 3 SD. Four pts did not respond to
treatment. One pt was not evaluable for response.
Median duration of response in brain was 10.5 weeks
(range, 6-48+ wks). Two pts with SD and 2 pts with MR
had previously received whole brain radiation therapy.
Three pts were taken off the study because of
progression of disease outside the brain including the
pt who had a CR in brain but progressed systemically.
Four pts are actively being treated in the study.
Conclusions: The combination of C and T seems to be
active and well tolerated for the treatment of brain
metastases from breast carcinoma. Further studies
should include the evaluation of this combination with
radiation and as adjuvant therapy in those pts who are
at high risk of developing brain metastases.
Wednesday, December 8, 2004 4:30 PM
Poster Session: Treatment: Chemotherapy -- New Drugs and Formulations (4:30 PM-7:00 PM)
Also this:
Pegylated liposomal doxorubicin plus temozolamide in the salvage treatment of brain metastases: The update.
Meeting: 2004 ASCO Annual Meeting
Category: Central Nervous System Tumors
SubCategory: CNS Tumors
Abstract No: 1576
Author(s): M. Caraglia, R. Addeo, R. Costanzo, L. Montella, V. Faiola, E. Capasso, S. Del Prete; S. Giovanni di Dio Hospital, Frattamaggiore, Italy
Abstract: Background:
It has been recently demonstrated that pegylated liposomal doxorubicin (Caelyx, PLD) can cross the brain-blood barrier with a consequent accumulation in primitive and secondary brain tumours. Moreover, temozolamide (TMZ) is a new imidazo-tetrazine that accumulates in brain tissue and is used alone or in combination with radiotherapy in the treatment of primary and secondary brain tumours. The two drugs have been already used in combination in a phase I cinical study in the treatment of advanced solid tumours.
Methods: We have evaluated the feasibility of the concomitant administration of TMZ and PLD in the treatment of brain mestastases and a preliminary evaluation of the activity was also performed. We have treated 12 consecutive patients (7 F and 5 M, mean age: 62.83 + 13.9 yrs; median age: 65.5 yrs) affected by brain metastases from different solid tumours (4 breast adenocarcinoma, 6 non small lung cancer, 1 melanoma, 1 ovarian cancer) with TMZ 1000 mg/m2 fractionated in 5 days and PLD 40 mg/m2 day 1 every 28 days. Nine out of 12 pts. have received previous whole brain irradiation plus TMZ.
Results: Thirty-four cycles were performed. Three grade II ad 8 grade I neutropenia (CTC), 2 grade II hand and foot syndrome, 8 grade I thrombocytopenia and 9 grade I alopecia were recorded. Nausea and vomiting or liver or renal toxicity were never observed in our series being the schedule well tolerated in all patients. Two CR and two PRs was recorded in the four patients with breast tumours, while a clinical benefit was achieved in other 4 patients (1 with melanoma and 3 with lung cancer). In the long-surviving pt. (overall survival, OS: 27+ months), who achieved CR, also a remission of a neoplastic pleural effusion was observed. Other 2 still alive pts. (breast and NSCLC, respectively), who achieved a PR and a SD, had an OS of 14 and 9 months, respectively.
Conclusions: the schedule was a well tolerated treatment (also in elder pts.) and has suggested an encouraging activity in brain metastases from breast.
SABCS ABSTRACT:
[San Antonio Breast Cancer Symposium]
[1079] Phase I study of capecitabine (C) in combination with temozolomide (T) in the treatment of patients with brain metastases from breast carcinoma.
Rivera E, Valero V, Francis D, Brewster A, Royce M, Esteva F, Murray JL, Pusztai L, Hortobagyi GN.. The University of Texas M.D. Anderson Cancer Center, Houston, TX
Background: T is an oral alkylating agent that is
currently being used for the treatment of primary
brain tumors due to its ability to cross the
blood-brain barrier. C has been approved for use in
the treatment of metastatic breast cancer patients who
have failed anthracyclines and taxanes. It is well
known that C crosses the blood-brain barrier and has
activity in the brain. Options are limited for
patients with brain metastases.
Materials and Methods: We evaluated the activity of
both drugs in combination for the treatment of brain
metastases not amenable to surgery. Patients were
allowed in the study if they had new onset brain
metastases from breast cancer, had declined radiation
therapy, and were neurologically stable. They were
also eligible if they had evidence of recurrence or
progression of brain metastases after whole brain or
stereotactic radiation therapy. C was started at 1800
mg/m2 in 2 divided doses. T was given at a starting
dose of 75 mg/m2 in one daily dose. Each drug was
given concomitantly every day for 5 days (day 1-5)
followed by 2 days of rest and restarted again for an
additional 5 days (days 8-12). Each cycle was repeated
every 21 days. We have enrolled a total of 16 pts — 6
pts at dose level 0 (C/T — 1800/75), 6 pts at dose
level 1 (C/T — 1800/100), and 4 pts at dose level 2
(C/T — 2000/100).
Results: Five pts had recurrent brain metastases and
had been previously treated with radiation therapy.
The median age is 51 yrs (range, 32-77). All pts had a
Zubrod performance status < 1. Ten pts were ER and/or
PR positive. No grade 4 toxicities have been reported.
Grade 3 toxicity includes headaches (2 pts), vomiting
(1 pt), constipation (2 pts), fatigue (2 pts),
nonneutropenic fever (1 pt). We have observed 1 CR, 1
PR, 6 MR, and 3 SD. Four pts did not respond to
treatment. One pt was not evaluable for response.
Median duration of response in brain was 10.5 weeks
(range, 6-48+ wks). Two pts with SD and 2 pts with MR
had previously received whole brain radiation therapy.
Three pts were taken off the study because of
progression of disease outside the brain including the
pt who had a CR in brain but progressed systemically.
Four pts are actively being treated in the study.
Conclusions: The combination of C and T seems to be
active and well tolerated for the treatment of brain
metastases from breast carcinoma. Further studies
should include the evaluation of this combination with
radiation and as adjuvant therapy in those pts who are
at high risk of developing brain metastases.
Wednesday, December 8, 2004 4:30 PM
Poster Session: Treatment: Chemotherapy -- New Drugs and Formulations (4:30 PM-7:00 PM)
Also this:
Pegylated liposomal doxorubicin plus temozolamide in the salvage treatment of brain metastases: The update.
Meeting: 2004 ASCO Annual Meeting
Category: Central Nervous System Tumors
SubCategory: CNS Tumors
Abstract No: 1576
Author(s): M. Caraglia, R. Addeo, R. Costanzo, L. Montella, V. Faiola, E. Capasso, S. Del Prete; S. Giovanni di Dio Hospital, Frattamaggiore, Italy
Abstract: Background:
It has been recently demonstrated that pegylated liposomal doxorubicin (Caelyx, PLD) can cross the brain-blood barrier with a consequent accumulation in primitive and secondary brain tumours. Moreover, temozolamide (TMZ) is a new imidazo-tetrazine that accumulates in brain tissue and is used alone or in combination with radiotherapy in the treatment of primary and secondary brain tumours. The two drugs have been already used in combination in a phase I cinical study in the treatment of advanced solid tumours.
Methods: We have evaluated the feasibility of the concomitant administration of TMZ and PLD in the treatment of brain mestastases and a preliminary evaluation of the activity was also performed. We have treated 12 consecutive patients (7 F and 5 M, mean age: 62.83 + 13.9 yrs; median age: 65.5 yrs) affected by brain metastases from different solid tumours (4 breast adenocarcinoma, 6 non small lung cancer, 1 melanoma, 1 ovarian cancer) with TMZ 1000 mg/m2 fractionated in 5 days and PLD 40 mg/m2 day 1 every 28 days. Nine out of 12 pts. have received previous whole brain irradiation plus TMZ.
Results: Thirty-four cycles were performed. Three grade II ad 8 grade I neutropenia (CTC), 2 grade II hand and foot syndrome, 8 grade I thrombocytopenia and 9 grade I alopecia were recorded. Nausea and vomiting or liver or renal toxicity were never observed in our series being the schedule well tolerated in all patients. Two CR and two PRs was recorded in the four patients with breast tumours, while a clinical benefit was achieved in other 4 patients (1 with melanoma and 3 with lung cancer). In the long-surviving pt. (overall survival, OS: 27+ months), who achieved CR, also a remission of a neoplastic pleural effusion was observed. Other 2 still alive pts. (breast and NSCLC, respectively), who achieved a PR and a SD, had an OS of 14 and 9 months, respectively.
Conclusions: the schedule was a well tolerated treatment (also in elder pts.) and has suggested an encouraging activity in brain metastases from breast.