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Orbital lymphoma: is it necessary to treat the entire orbit?
Proceedings of the 45th Annual ASTRO Meeting
1049
15-Year Results of Total Skin Electron Beam (TSEB) Radiation as First-Line Monotherapy for Newly Diagnosed Stage IA–IB Mycosis Fungoides (MF)
G.W. Jones,1,2 R. Wong,1,2 J. Kastikainen,2 N. Farrar,2 L. Fox-Goguen,2 R. Sur1,2 Medicine, McMaster University, Hamilton, ON, Canada, 2Radiation Oncology, Hamilton Regional Cancer Centre, Hamilton, ON, Canada 1
Purpose/Objective: Eighty percent of new MF cases are IA and IB. TSEB is a controversial first-line management because very long-term data with sufficient numbers of patients have not yet been published. Recent advances to the TSEB-based strategy include more intense consensus TSEB (J Am Acad Derm 2002;47:364), supplemental perineum-buttock radiation, and adjuvant PUVA (IJROBP 1997;35:1027). Avoiding a first recurrence is of clinical importance for psychological reasons as well as potentially for long-term disease control. However, the impact of these advances to the TSEB-based strategy, on disease and patient outcomes, must exceed both benchmark short- and long-term results from historical TSEB, if those advances are to be of real clinical value. Materials/Methods: One hundred twenty-three IA and 75 IB newly diagnosed MF patients (1972–2001) received TSEB without supplemental radiation or adjuvant therapy. Non-response and relapse mean positive clinical examination plus skin biopsies. Treatment for relapse followed a care path. Single-lesions received local superficial radiotherapy (LR); minor diffuse spots, topical steroid (TS) for a month; more extensive spots, nitrogen mustard for 8 months (NM), or PUVA for 6 months since 1993. LR consisted of a small standard field, 100 kV or 6 –9 MeV electrons, 4-to-8 Gy in 1– 4 fractions. Time-to-Second Progression (TTSP) was measured from commencing TSEB to first evidence of failure of the second-line therapy. 50% of patients with such a second progression were simply given an additional short course of their second-line therapies (e.g. another LR for a new single lesion); and the remainder received another topical therapy, based on disease extent and patient preference. Results: Average age was 54 (18 –91); 41% were female; average skin surface involvement was 13% (4.5% for IA; 24% for IB). Average surface dose of TSEB was 33.7 Gray (to 1980, 30 Gy; then 35 Gy), using 3– 4 MeV electrons. Plots show a 15-yr overall survival of 88% for IA, and 76% for IB (p⫽0.05). Fifteen-year MF-risk of death was 1% for IA, and 7% for IB (p⫽0.54). Multivariate analyses showed outcomes associated with both lower stage and greater radiation dose (multivariate p-values): for remission—IA (0.02), dose (0.0017); for progression-free duration—IA (0.004), dose (0.0016); and for survival—IA (0.06), dose (0.01). In follow-up, 54% of the IA cohort and 71% of the IB cohort relapsed. Therapies for relapse in the IA cohort were 41% LR, 26% TS, 23% NM and 11% PUVA; and for IB they were 19% LR, 13% TS, 49% NM, and 19% PUVA. Control of disease (no further relapse) was best achieved with LR (n⫽27, 65% at 10 yr following LR) and NM (n⫽15, 65% at 10 yr following NM) and in the IA cohort. 15-yr TTSP for the IA cohort was 65%; for the IB cohort, 40% (p⫽0.004). Overall then, about 50% of patients were estimated to experience disease control through 15 yr of follow-up, and spending 97% of those 15 yr without disease, treatments and toxicities. Conclusions: Long-term results with a TSEB strategy for IA–IB MF, with judicious choice of second-line therapy, demonstrate acceptable cancer control. Also, regression analyses give further evidence supporting the use of a consensus TSEB (35 Gy gave superior clinical results compared to 30 Gy, though with only 3– 4 MeV electrons). The present treatment protocol in Hamilton combines consensus TSEB (35 Gy and 4.4 MeV electrons), supplemental perineum-buttock LR during TSEB and guided by thermoluminescent dosimetry to eliminate technical failures at that site, and 6 months of adjuvant PUVA. Early results are 100% complete remission with a 2-yr progression-free survival also at 100% (with p⫽0.05 for contrast with historical TSEB). Though these results are excellent, maturing results with this protocol must still exceed the benchmark 50% 15-yr disease control to justify it on clinical and economic grounds.
1050
Orbital Lymphoma: Is It Necessary To Treat The Entire Orbit?
1
T. Rabin, Z. Symon,1 N. Rosen,2 J. Goffman,1 D. Alezra,1 R. Pfeffer1 Oncology, Sheba Medical Center, Tel Hashomer, Israel, 2Ophthalmology, Sheba Medical Center, Tel Hashomer, Israel
1
Purpose/Objective: Orbital lymphomas are usually low grade tumors that respond to relatively low doses of radiotherapy. In 1997 we began a policy of using conformal CT-based radiotherapy to treat patients with orbital lymphoma. Patients with circumscribed orbital lesions received partial orbit irradiation in order to reduce the dose and toxicity to the unaffected areas of the orbit. We compare here the outcome and toxicity of radiotherapy in the group of patients with circumscribed orbital lymphomas considered to be suitable for partial orbit irradiation with the group of patients with more widespread lesions requiring standard whole orbit irradiation. Materials/Methods: A retrospective study was carried out on the radiotherapy and ophthalmology clinic charts of 22 consecutive patients who received treatment for orbital lymphoma in the Radiotherapy Institute at Sheba Medical Center between 1997 and 2002. None of the patients had extra-orbital disease at presentation and none of them received chemotherapy. Several patients received varying doses of corticosteroids prior to or during radiotherapy. Histology was B-cell lymphoma (19 patients), MALT (2 patients), and Mantle cell lymphoma (1 patient). There were 6 males and 16 females of age range 20 –92 (median 58) years. The dose of radiotherapy delivered was 2340 –3200 (median 2520) cGy usually in 180 cGy daily fractions. All patients had contrast enhanced CT scans of the orbit and underwent mask immobilization and CT-based treatment planning. The PTV was the lesion seen on CT with 1-cm margins. Twelve patients who had circumscribed lesions received partial orbit radiotherapy, usually via oblique fields. Ten patients with more widespread lesions requiring irradiation of the entire orbit were usually treated with direct anterior radiation fields. Results: Patients have been followed up at regular intervals for 7– 68 months (median 32 months). Acute toxicity consisted of conjunctivitis observed in 3 patients receiving AP fields to the entire orbit, and in 4 patients receiving partial orbit irradiation. Tearing was seen in 8 patients in each group. Late toxicity included dry eye in 4 (33%) patients treated with partial orbit irradiation and in 1 (10%) patient receiving whole orbit irradiation. Corneal erosion was seen in one patient receiving partial orbit irradiation. One patient who received whole orbit irradiation has asymptomatic retinal scarring. All patients retained good vision except for one patient who presented with deteriorating vision and became blind in the affected eye during the first week of radiotherapy. Four out of 12 (33%) patients in the group treated with partial orbit irradiation developed intra-orbital
S291
S292
I. J. Radiation Oncology
● Biology ● Physics
Volume 57, Number 2, Supplement, 2003
recurrence in previously uninvolved areas not included in the initial target volume. Three were re-irradiated with anterior fields to the whole orbit and one underwent resection alone. All of these patients are free of disease at the latest follow up. One out of ten (10%) patients treated with whole orbit irradiation developed a recurrence in the skin and soft tissues lateral to the orbit. She is disease free after further radiotherapy to these sites. Conclusions: In our small retrospective study patients with orbital lymphoma treated with radiotherapy to partial orbit volumes suffered from an unacceptable 33% incidence of intra-orbital recurrence outside of the PTV. This may be explained by the existence of subclininal disease in seemingly unaffected intra-orbital areas. Reducing the PTV to exclude uninvolved intra-orbital areas did not result in less toxicity than whole orbit irradiation. Doses of irradiation of the order of 25 Gy are effective to treat most low-grade orbital lymphomas. These doses result in minimal morbidity even when delivered to the entire orbit. Patients with orbital lymphoma should therefore be treated with low dose radiation to the entire orbit.
1051
Low Dose Total Body Irradiation (TBI) In Outpatient Non-Myeloablative Bone Marrow Transplantation
R.M. Macklis,1 M. Kalaycio,2 R. Sobecks,2 B. Pohlman,2 S. Brown,2 B. Bolwell2 Radiation Oncology, Cleveland Clinic, Cleveland, OH, 2Medical Oncology, Cleveland Clinic, Cleveland, OH
1
Purpose/Objective: Myeloablative Bone Marrow Transplantation (BMT) using either TBI or dose-intense chemotherapy has now become standard management for refractory hematopoietic tumors. However, standard preparative regimens often result in unacceptably high risks of pulmonary, hepatic, and renal toxicity. For allogeneic BMT, these risks are compounded by the risk of graft rejection or graft v. host disease (GVHD). Increased immunosuppression used to prevent GVHD has unfortunately resulted in higher rates of disease recurrence, leading many investigators to conclude that a large part of the therapeutic benefit of BMT resides in the immunologic response engendered by a minor degree of GVHD (the graft v. tumor effect, GVT). This realization has lead to a radical new approach to BMT in which the intensity of the prep regimen is deliberately decreased below the level required for marrow ablation. The chimerism produced by non-myeloablative BMT (NMBMT) is modulated to optimize GVT while still minimizing organ toxicity. Low dose TBI (2Gy) in conjunction with moderate dose fludarabine (FLU) represents one promising regimen for NMBMT. The NMBMT cohort has now become the largest group of TBI-prepared transplant patients at our institution. Materials/Methods: Forty-one patients have undergone NMBMT since 2000. Indications for NMBMT have included NHL, myelodysplastic syndromes, Waldenstroms, AML, CML, myeloma, CLL, and renal cell ca. 35 of these patients are evaluable with at least three months of follow-up. Twenty-seven patients received sibling stem cells, whereas 8 patients received matched unrelated donor (MUD) stem cells or marrow through the national marrow transplant registry. All patients received TBI (2 Gy) delivered using a 6 MV linear accelerator, dose rate 10 –20 cGy per minute with beam spoiler and TLD dosimetry. The FLU was delivered in the 3 days prior to TBI, and the donor stem cells were infused the following day. The NMBMT was carried out entirely in the outpatient environment except for complications. Results: Despite the fact that 8 patients had previously undergone a failed autotransplant using either high dose Busulfan/ Cytoxan or TBI, no patient suffered profound pulmonary, renal, or hepatic toxicity. The majority of these re-transplant patients did show some low level of serious but non-life threatening organ toxicity, with 6/8 showing a modest decrease in FEV1 levels (2–21%). For the 27 patients transplanted using well matched sibling stem cells, all patients engrafted with an average day 21 ANC of 7.17 and platelet count of 145 K. Seven patients remain in CR with a median follow up time of ⬎2 years. One patient is currently alive with disease and 11 patients have expired (6 from GVHD and 5 from progression). For the 8 patients undergoing NMBMT using MUD transplants, no patients are currently alive in CR. Four of these patients experienced primary graft failure and 3 expired of GVHD. Conclusions: (1) NMBMT utilizing low dose TBI and FLU represents an important new approach to allogeneic BMT, with substantially lower toxicities than fully ablative transplantation. The ability to conduct this sort of transplant program in an outpatient environment greatly expands the flexibility and dramatically decreases the costs of the program. (2) Radiation-related organ toxicity appears manageable, even in patients who have previously undergone a failed high-dose BMT. (3) When sibling marrow is available, the NMBMT approach yields intermediate-term DFS rates on the order of 33%. However, control rates using MUD donors currently appear unsatisfactory. Our next generation of NMBMT protocols will explore somewhat more intensive preparative regimens incorporating either higher doses of TBI (perhaps 4 Gy) or targeted radiation boosts delivered via external beam irradiation or anti-CD20 radio-immunotherapy. (4) Diseases that have shown especially promising early results with the current regimen include NHL and CML. Diseases in which our current preparative regimen appears unsatisfactory include renal cell carcinoma, multiple myeloma, and AML.
1052
C225 Anti-EGFR (Epidermal Growth Factor Receptor) Antibody Enhances the Efficacy of Docetaxel Chemoradiotherapy
E. Nakata,3,1 U. Raju,1 N. Hunter,1 K. Mason,1 Z. Fan,4 K.K. Ang,2 S. Yamada,3 L. Milas1 1 Experimental Radiation Oncology - 066, UT MD Anderson Cancer Center, Houston, TX, 2Division of Radiation Oncology - 097, UT MD Anderson Cancer Center, Houston, TX, 3Radiation Oncology, Tohoku University Medical School, Sendai, Japan, 4Experimental Therapeutics, UT MD Anderson Cancer Center, Houston, TX Purpose/Objective: Our earlier studies showed that C225 anti-EGFR antibody enhances tumor radioresponse (Clin Cancer Res 200;6:701–708), and studies by others demonstrated that this antibody improves the antitumor efficacy of a number of chemotherapeutic agents. Because of increased use of chemoradiotherapy in cancer treatment, it is important to determine whether C225 also enhances chemoradiotherapy. This study assessed the effect of C225 on tumor response when combined with docetaxel plus single or fractionated radiation. Materials/Methods: MDA468 human adenocarcinoma cells growing as xenografts in the right hind leg of nude mice were used. Mice bearing 8 mm tumors were treated with C225 antibody at a dose of 1 mg given ip once or twice 3 days apart, 10 mg/kg docetaxel given iv, and/or local tumor irradiation of 8 Gy single dose or fractionated irradiation consisting of 2 Gy daily for 5 days. When all 3 agents were combined, C225 was given 6 h before docetaxel and radiation was given 24 h after docetaxel. The treatment endpoint was tumor growth delay.
1049
15-Year Results of Total Skin Electron Beam (TSEB) Radiation as First-Line Monotherapy for Newly Diagnosed Stage IA–IB Mycosis Fungoides (MF)
G.W. Jones,1,2 R. Wong,1,2 J. Kastikainen,2 N. Farrar,2 L. Fox-Goguen,2 R. Sur1,2 Medicine, McMaster University, Hamilton, ON, Canada, 2Radiation Oncology, Hamilton Regional Cancer Centre, Hamilton, ON, Canada 1
Purpose/Objective: Eighty percent of new MF cases are IA and IB. TSEB is a controversial first-line management because very long-term data with sufficient numbers of patients have not yet been published. Recent advances to the TSEB-based strategy include more intense consensus TSEB (J Am Acad Derm 2002;47:364), supplemental perineum-buttock radiation, and adjuvant PUVA (IJROBP 1997;35:1027). Avoiding a first recurrence is of clinical importance for psychological reasons as well as potentially for long-term disease control. However, the impact of these advances to the TSEB-based strategy, on disease and patient outcomes, must exceed both benchmark short- and long-term results from historical TSEB, if those advances are to be of real clinical value. Materials/Methods: One hundred twenty-three IA and 75 IB newly diagnosed MF patients (1972–2001) received TSEB without supplemental radiation or adjuvant therapy. Non-response and relapse mean positive clinical examination plus skin biopsies. Treatment for relapse followed a care path. Single-lesions received local superficial radiotherapy (LR); minor diffuse spots, topical steroid (TS) for a month; more extensive spots, nitrogen mustard for 8 months (NM), or PUVA for 6 months since 1993. LR consisted of a small standard field, 100 kV or 6 –9 MeV electrons, 4-to-8 Gy in 1– 4 fractions. Time-to-Second Progression (TTSP) was measured from commencing TSEB to first evidence of failure of the second-line therapy. 50% of patients with such a second progression were simply given an additional short course of their second-line therapies (e.g. another LR for a new single lesion); and the remainder received another topical therapy, based on disease extent and patient preference. Results: Average age was 54 (18 –91); 41% were female; average skin surface involvement was 13% (4.5% for IA; 24% for IB). Average surface dose of TSEB was 33.7 Gray (to 1980, 30 Gy; then 35 Gy), using 3– 4 MeV electrons. Plots show a 15-yr overall survival of 88% for IA, and 76% for IB (p⫽0.05). Fifteen-year MF-risk of death was 1% for IA, and 7% for IB (p⫽0.54). Multivariate analyses showed outcomes associated with both lower stage and greater radiation dose (multivariate p-values): for remission—IA (0.02), dose (0.0017); for progression-free duration—IA (0.004), dose (0.0016); and for survival—IA (0.06), dose (0.01). In follow-up, 54% of the IA cohort and 71% of the IB cohort relapsed. Therapies for relapse in the IA cohort were 41% LR, 26% TS, 23% NM and 11% PUVA; and for IB they were 19% LR, 13% TS, 49% NM, and 19% PUVA. Control of disease (no further relapse) was best achieved with LR (n⫽27, 65% at 10 yr following LR) and NM (n⫽15, 65% at 10 yr following NM) and in the IA cohort. 15-yr TTSP for the IA cohort was 65%; for the IB cohort, 40% (p⫽0.004). Overall then, about 50% of patients were estimated to experience disease control through 15 yr of follow-up, and spending 97% of those 15 yr without disease, treatments and toxicities. Conclusions: Long-term results with a TSEB strategy for IA–IB MF, with judicious choice of second-line therapy, demonstrate acceptable cancer control. Also, regression analyses give further evidence supporting the use of a consensus TSEB (35 Gy gave superior clinical results compared to 30 Gy, though with only 3– 4 MeV electrons). The present treatment protocol in Hamilton combines consensus TSEB (35 Gy and 4.4 MeV electrons), supplemental perineum-buttock LR during TSEB and guided by thermoluminescent dosimetry to eliminate technical failures at that site, and 6 months of adjuvant PUVA. Early results are 100% complete remission with a 2-yr progression-free survival also at 100% (with p⫽0.05 for contrast with historical TSEB). Though these results are excellent, maturing results with this protocol must still exceed the benchmark 50% 15-yr disease control to justify it on clinical and economic grounds.
1050
Orbital Lymphoma: Is It Necessary To Treat The Entire Orbit?
1
T. Rabin, Z. Symon,1 N. Rosen,2 J. Goffman,1 D. Alezra,1 R. Pfeffer1 Oncology, Sheba Medical Center, Tel Hashomer, Israel, 2Ophthalmology, Sheba Medical Center, Tel Hashomer, Israel
1
Purpose/Objective: Orbital lymphomas are usually low grade tumors that respond to relatively low doses of radiotherapy. In 1997 we began a policy of using conformal CT-based radiotherapy to treat patients with orbital lymphoma. Patients with circumscribed orbital lesions received partial orbit irradiation in order to reduce the dose and toxicity to the unaffected areas of the orbit. We compare here the outcome and toxicity of radiotherapy in the group of patients with circumscribed orbital lymphomas considered to be suitable for partial orbit irradiation with the group of patients with more widespread lesions requiring standard whole orbit irradiation. Materials/Methods: A retrospective study was carried out on the radiotherapy and ophthalmology clinic charts of 22 consecutive patients who received treatment for orbital lymphoma in the Radiotherapy Institute at Sheba Medical Center between 1997 and 2002. None of the patients had extra-orbital disease at presentation and none of them received chemotherapy. Several patients received varying doses of corticosteroids prior to or during radiotherapy. Histology was B-cell lymphoma (19 patients), MALT (2 patients), and Mantle cell lymphoma (1 patient). There were 6 males and 16 females of age range 20 –92 (median 58) years. The dose of radiotherapy delivered was 2340 –3200 (median 2520) cGy usually in 180 cGy daily fractions. All patients had contrast enhanced CT scans of the orbit and underwent mask immobilization and CT-based treatment planning. The PTV was the lesion seen on CT with 1-cm margins. Twelve patients who had circumscribed lesions received partial orbit radiotherapy, usually via oblique fields. Ten patients with more widespread lesions requiring irradiation of the entire orbit were usually treated with direct anterior radiation fields. Results: Patients have been followed up at regular intervals for 7– 68 months (median 32 months). Acute toxicity consisted of conjunctivitis observed in 3 patients receiving AP fields to the entire orbit, and in 4 patients receiving partial orbit irradiation. Tearing was seen in 8 patients in each group. Late toxicity included dry eye in 4 (33%) patients treated with partial orbit irradiation and in 1 (10%) patient receiving whole orbit irradiation. Corneal erosion was seen in one patient receiving partial orbit irradiation. One patient who received whole orbit irradiation has asymptomatic retinal scarring. All patients retained good vision except for one patient who presented with deteriorating vision and became blind in the affected eye during the first week of radiotherapy. Four out of 12 (33%) patients in the group treated with partial orbit irradiation developed intra-orbital
S291
S292
I. J. Radiation Oncology
● Biology ● Physics
Volume 57, Number 2, Supplement, 2003
recurrence in previously uninvolved areas not included in the initial target volume. Three were re-irradiated with anterior fields to the whole orbit and one underwent resection alone. All of these patients are free of disease at the latest follow up. One out of ten (10%) patients treated with whole orbit irradiation developed a recurrence in the skin and soft tissues lateral to the orbit. She is disease free after further radiotherapy to these sites. Conclusions: In our small retrospective study patients with orbital lymphoma treated with radiotherapy to partial orbit volumes suffered from an unacceptable 33% incidence of intra-orbital recurrence outside of the PTV. This may be explained by the existence of subclininal disease in seemingly unaffected intra-orbital areas. Reducing the PTV to exclude uninvolved intra-orbital areas did not result in less toxicity than whole orbit irradiation. Doses of irradiation of the order of 25 Gy are effective to treat most low-grade orbital lymphomas. These doses result in minimal morbidity even when delivered to the entire orbit. Patients with orbital lymphoma should therefore be treated with low dose radiation to the entire orbit.
1051
Low Dose Total Body Irradiation (TBI) In Outpatient Non-Myeloablative Bone Marrow Transplantation
R.M. Macklis,1 M. Kalaycio,2 R. Sobecks,2 B. Pohlman,2 S. Brown,2 B. Bolwell2 Radiation Oncology, Cleveland Clinic, Cleveland, OH, 2Medical Oncology, Cleveland Clinic, Cleveland, OH
1
Purpose/Objective: Myeloablative Bone Marrow Transplantation (BMT) using either TBI or dose-intense chemotherapy has now become standard management for refractory hematopoietic tumors. However, standard preparative regimens often result in unacceptably high risks of pulmonary, hepatic, and renal toxicity. For allogeneic BMT, these risks are compounded by the risk of graft rejection or graft v. host disease (GVHD). Increased immunosuppression used to prevent GVHD has unfortunately resulted in higher rates of disease recurrence, leading many investigators to conclude that a large part of the therapeutic benefit of BMT resides in the immunologic response engendered by a minor degree of GVHD (the graft v. tumor effect, GVT). This realization has lead to a radical new approach to BMT in which the intensity of the prep regimen is deliberately decreased below the level required for marrow ablation. The chimerism produced by non-myeloablative BMT (NMBMT) is modulated to optimize GVT while still minimizing organ toxicity. Low dose TBI (2Gy) in conjunction with moderate dose fludarabine (FLU) represents one promising regimen for NMBMT. The NMBMT cohort has now become the largest group of TBI-prepared transplant patients at our institution. Materials/Methods: Forty-one patients have undergone NMBMT since 2000. Indications for NMBMT have included NHL, myelodysplastic syndromes, Waldenstroms, AML, CML, myeloma, CLL, and renal cell ca. 35 of these patients are evaluable with at least three months of follow-up. Twenty-seven patients received sibling stem cells, whereas 8 patients received matched unrelated donor (MUD) stem cells or marrow through the national marrow transplant registry. All patients received TBI (2 Gy) delivered using a 6 MV linear accelerator, dose rate 10 –20 cGy per minute with beam spoiler and TLD dosimetry. The FLU was delivered in the 3 days prior to TBI, and the donor stem cells were infused the following day. The NMBMT was carried out entirely in the outpatient environment except for complications. Results: Despite the fact that 8 patients had previously undergone a failed autotransplant using either high dose Busulfan/ Cytoxan or TBI, no patient suffered profound pulmonary, renal, or hepatic toxicity. The majority of these re-transplant patients did show some low level of serious but non-life threatening organ toxicity, with 6/8 showing a modest decrease in FEV1 levels (2–21%). For the 27 patients transplanted using well matched sibling stem cells, all patients engrafted with an average day 21 ANC of 7.17 and platelet count of 145 K. Seven patients remain in CR with a median follow up time of ⬎2 years. One patient is currently alive with disease and 11 patients have expired (6 from GVHD and 5 from progression). For the 8 patients undergoing NMBMT using MUD transplants, no patients are currently alive in CR. Four of these patients experienced primary graft failure and 3 expired of GVHD. Conclusions: (1) NMBMT utilizing low dose TBI and FLU represents an important new approach to allogeneic BMT, with substantially lower toxicities than fully ablative transplantation. The ability to conduct this sort of transplant program in an outpatient environment greatly expands the flexibility and dramatically decreases the costs of the program. (2) Radiation-related organ toxicity appears manageable, even in patients who have previously undergone a failed high-dose BMT. (3) When sibling marrow is available, the NMBMT approach yields intermediate-term DFS rates on the order of 33%. However, control rates using MUD donors currently appear unsatisfactory. Our next generation of NMBMT protocols will explore somewhat more intensive preparative regimens incorporating either higher doses of TBI (perhaps 4 Gy) or targeted radiation boosts delivered via external beam irradiation or anti-CD20 radio-immunotherapy. (4) Diseases that have shown especially promising early results with the current regimen include NHL and CML. Diseases in which our current preparative regimen appears unsatisfactory include renal cell carcinoma, multiple myeloma, and AML.
1052
C225 Anti-EGFR (Epidermal Growth Factor Receptor) Antibody Enhances the Efficacy of Docetaxel Chemoradiotherapy
E. Nakata,3,1 U. Raju,1 N. Hunter,1 K. Mason,1 Z. Fan,4 K.K. Ang,2 S. Yamada,3 L. Milas1 1 Experimental Radiation Oncology - 066, UT MD Anderson Cancer Center, Houston, TX, 2Division of Radiation Oncology - 097, UT MD Anderson Cancer Center, Houston, TX, 3Radiation Oncology, Tohoku University Medical School, Sendai, Japan, 4Experimental Therapeutics, UT MD Anderson Cancer Center, Houston, TX Purpose/Objective: Our earlier studies showed that C225 anti-EGFR antibody enhances tumor radioresponse (Clin Cancer Res 200;6:701–708), and studies by others demonstrated that this antibody improves the antitumor efficacy of a number of chemotherapeutic agents. Because of increased use of chemoradiotherapy in cancer treatment, it is important to determine whether C225 also enhances chemoradiotherapy. This study assessed the effect of C225 on tumor response when combined with docetaxel plus single or fractionated radiation. Materials/Methods: MDA468 human adenocarcinoma cells growing as xenografts in the right hind leg of nude mice were used. Mice bearing 8 mm tumors were treated with C225 antibody at a dose of 1 mg given ip once or twice 3 days apart, 10 mg/kg docetaxel given iv, and/or local tumor irradiation of 8 Gy single dose or fractionated irradiation consisting of 2 Gy daily for 5 days. When all 3 agents were combined, C225 was given 6 h before docetaxel and radiation was given 24 h after docetaxel. The treatment endpoint was tumor growth delay.