|
Treatments
> Refractory Disease (Overcoming Drug Resistance)
Last update: 05/12/2008 |
Protocols for Refractory Lymphomas:
CLL | Aggressive/Diffuse | CNS
Lymphoma | PMBCL | Follicular
| Hodgkins | Mantle Cell |
Marginal Zone/MALT
T-cell | NHL Unspecified
| Low Counts and not Eligible for SCT
ALSO
SEE: About
Drug Resistance | Treatments
for Elderly | Eligibility Factors | Resources
Clinical Trials for Refractory Lymphomas
| Pipeline
Here
we provide resources for patients and professionals to use when searching
for information about treatment protocols that may help to overcome refractory disease - disease that is resistant, so far, to
treatment. The references within are not necessarily up-to-date - so
we have provided  Topic Searches of outside resources
to help you to locate new information published elsewhere.
It's
important to have expert guidance on treatments. One important
goal for the patient is understand the
risks of the disease and the potential risks
and benefits of the treatments under consideration. For
example, it can be appropriate - even essential - to use higher-risk aggressive
therapies to treat high-risk disease in order to potentially
eradicate the disease or produce a durable remission, but
only if there is at least some data to show the goal of treatment is
realistic for your diagnosis, and the risks are appropriate to your
general health, age, treatment history, etc..
Consult with at least one outside expert to obtain opinion and rationales about your
treatment options. Note: The rationales of experts can be
more useful to you than opinion, especially when you receive
different opinions from different experts.
Clinical
Trials? If the data for standard approaches specific to your
diagnosis are not strong, consideration of investigational
therapies becomes more reasonable. However, it does not follow
that investigational therapies will always be safer or more
effective than standard therapies. Therefore, you must read the
Informed Consent documents carefully and seek objective opinions and
the guidance of your treating physician. That said, you do not need
your physician's permission to review clinical trials, contact
clinical investigators, or participate in clinical trials.
However, it is best to ask the investigator of the study to consult
with your treating physician, and for you to consult independent
experts regarding the potential risks and benefits of the investigational
protocol you are considering. See Locating Experts in the
Field.
Questions you
might ask the doctors you consult
*
What is the most realistic goal of
treatment?
Cure? Durable remission?
Management with least toxicity? Pain relief? Other?
* What percentage of patients -
specific to my diagnosis, health, treatment history - have had a durable remission following
the approach you are recommending? What are the risks of
this treatment?
May I have a copy of the published data you
are basing the recommendation on?
* What is the prognosis for my diagnosis for management therapies
- using the least toxic therapies, as needed? Is this approach realistic for
my diagnosis and the clinical details and history of my
case?
* What protocols do you recommend and
what advantages do each have relative to other treatment
protocols?
* What investigational protocols do
you recommend, and why?
See Also: Clinical-trials-for-me?
PDF
-
Protocols for Refractory Lymphomas by Disease
Subtype
Note: This is a work in progress. We update this list in response to visitor inquires.
CLL- Relapsed / Refractory
(or SLL)
Treatment
Search
for relapsed CLL PubMed
| ASCO.org
Clinical
Trial Search for CNS lymphoma ClinicalTrials.gov
Also
see NHL - unspecified | PubMed
| ClinicalTrials.gov
Stem Cell Transplantation
Chemotherapy-based
protocols
 |
Bendamustine ncbi.nlm.nih.gov
|
|
Nipent®/Cytoxan®/Rituxan® Shows
High Activity in Previously Treated CLL or Low-Grade NHL cancerconsultants.com
|
|
Treanda (Bendamustine) Full Prescribing information: FDA
as PDF file |
|
Low-dose
fludarabine and cyclophosphamide in elderly patients with
B-cell chronic lymphocytic leukemia refractory to conventional
therapy. Haematologica. 2000 Dec;85(12):1268-70. PMID:
11114133 |
|
Oxaliplatin, Fludarabine,
Cytarabine, and Rituxan combination therapy
in patients with Richter's syndrome or fludarabine-refractory CLL.
J Clin Oncol. 2008 Jan 10;26(2):196-203. PMID: 18182662 |
|
Rituximab with
Cladribine PMID: 16948126
The RC and RCC regimens were highly effective and well
tolerated modalities of treatment in
heavily pretreated patients
with indolent lymphoproliferative disorders. |
Novel / Targeted Therapies
See
also Pipeline
Return to top
CNS Lymphoma
Treatment
Search
for relapsed CNS lymphoma PubMed
| ASCO.org
Clinical
Trial Search for CNS lymphoma ClinicalTrials.gov
See
also Pipeline
| Intensive Chemotherapy Followed by Hematopoietic Stem-Cell Rescue for Refractory and Recurrent Primary CNS and Intraocular Lymphoma: Societe Francaise de Greffe de Moelle Osseuse-Therapie
Cellulaire. J Clin Oncol. 2008 Apr 14; PMID: 18413641
The respective median progression-free survival (PFS) times
after IC + HCR were 11.6 and 41.1 months. The 2-year overall
survival probability was 45% in the whole population and 69% among
the 27 patients who received IC + HCR. The 2-year PFS probability
was 43% among all the patients and 58% in the IC + HCR
subpopulation. CONCLUSION: IC + HCR is an effective treatment for
refractory and recurrent PCNSL. |
Primary Mediastinal B cell
Lymphoma (PMBCL)
See
also Pipeline
Return to top
Aggressive (such as Diffuse Large B Cell) -
refractory / primary refractory
Also
see NHL - unspecified | PubMed
| ClinicalTrials.gov
Treatment
Search for relapsed aggressive lymphoma PubMed
| ASCO.org Clinical
Trial Search for relapsed aggressive / DLBCL lymphoma
ClinicalTrials.gov
/ ClinicalTrials.gov
Stem Cell Transplant (SCT) for relapsed aggressive
lymphoma
|
Topic
Search |
|
Autologous
SCT: The International Prognostic Index predicts for outcome
following autologous stem cell transplantation in patients with
relapsed and primary refractory intermediate-grade lymphoma. Bone
Marrow Transplant. 1999 Mar;23(6):561-7. PMID:
10217186 | Related
articles |
|
Concurrent
high-dose Rituxan before and after
autologous stem-cell transplantation
PMID:
15800314 |
Chemotherapy-based
protocols
| Bendamustine
(Treanda) Topic
Search |
| Bendamustine
(Treanda) is effective in relapsed or refractory aggressive
non-Hodgkin’s lymphoma cancerconsultants.com
|
|
High-Dose Celecoxib
and Metronomic
"Low-dose" Cyclophosphamide clinicalcancerresearch
|
|
Cyclophosphamide, Cytarabine
and Methotrexate Regimen Followed
by Stem Cell Transplantation cancerconsultants.com |
|
Gallium nitrate,
Rituxan and Dexamethasone ASCO
2006 |
|
Gemcitabine, Ifosfamide, Oxaliplatin and Rituximab
(R-GIFOX) ASH2005 |
|
High-Dose Celecoxib
and Metronomic
"Low-dose" Cyclophosphamide clinicalcancerresearch
|
|
ICE: Ifosfamide,
carboplatin, etoposide
PMID: 12736224
| Abstracts |
| ICE +
Rituxan: PMID:
14739217 | Related articles
| Free
full text - Bloodjournal.org |
|
Ifosfamide,
Epirubicin and Etoposide (IEV) PMID:
15370212 |
| Metronomic
chemotherapy (low/continuous dosing). Topic
Search |
| Mitoxantrone,
carboplatin, cytosine arabinoside, and methylprednisolone followed
by
autologous peripheral blood stem cell transplantation (MiCMA):
[effective] PMID:
16419074
|
| Pixantrone
Pixantrone: A New Agent with Activity in Non-Hodgkin's Lymphoma cancerpublications.com
ClinicalTrials.gov |
|
R-GEMOX Rituxan, gemcitabine, and
oxaliplatin Medscape
[18] El-Gnaoui T, Joly B, Dupuis J, et al. Rituximab, gemcitabine and oxaliplatin
(R-GEMOX): Abstract 6592. |
| Sequential
Doxorubicin and Topotecan in relapsed/refractory aggressive Burkitt's
/ DLBCL:
Results of CALGB 59906. Leuk
Lymphoma. 2006 Aug;47(8):1511-7. PMID:
16966261 |
Novel /
Targeted therapies for aggressive lymphomas
See
also Pipeline
| Radioimmunotherapy
 |
Radioimmunotherapy
(Bexxar or Zevalin)
|
|
|
Rituxan for aggressive non-Hodgkin's lymphomas relapsing after or refractory to
auto SCT
PMID:
12416894
|
Return to top
Follicular lymphoma - Refractory / Transformed
Also
see NHL unspecified
Treatment
Search for relapsed follicular lymphoma Topic
Search | ASCO.org
Treatment
Search for transformed follicular lymphoma Topic
Search | ASCO.org
Clinical
Trial Search for relapsed follicular lymphoma ClinicalTrials.gov
Clinical
Trial Search for relapsed follicular lymphoma ClinicalTrials.gov
Stem Cell Transplantation
(SCT)
Allogeneic type (from
donor) Topic
Search | PAL
|
Non-Myeloablative
(mini) Topic
Search
"non-myeloablative" means pretreatment (conditioning
phase of treatment) that has lower
toxicity and does not ablate
(kill off) the myeloid cells in the marrow. Often called a
mini-transplant. "Allogeneic" means from a donor,
in this case an HLA-identical sibling.
"Hematopoietic" means the process of forming blood cells
from stem cells in the bone marrow. |
Autologous
cell transplantation PubMed
abstracts | Topic
Search | PAL
|
High-dose therapy with autologous
haematopoietic support in patients with transformed
follicular lymphoma: a study of 27 patients from a single center.
Ann Oncol. 1998 Aug;9(8):865-9. PMID: 9789609 - PubMed
| Abstracts |
Radioimmunotherapy
|
Radioimmunotherapy
(Bexxar or Zevalin)
|
|
Bexxar
High-dose radioimmunotherapy (Bexxar) versus conventional
high-dose therapy and autologous hematopoietic stem cell
transplantation for relapsed follicular non-Hodgkin's lymphoma: a
multivariable cohort analysis. Blood. 2003 May 15 PMID: 12750161
PubMed
| Abstracts
| PAL
|
|
Bexxar for
transformed fNHL Topic
Search |
|
Bexxar
in Patients With Relapsed or Refractory Indolent Non-Hodgkin's
Lymphoma:
Australian Multicenter Phase II Clinical Study. J Clin
Oncol. 2006 Aug 28; PMID:
16940276 |
|
Radioimmunotherapy of relapsed non-Hodgkin's lymphoma with
Zevalin, Review. PMID: 10541376 |
| Zevalin
for transformed fNHL |
Chemotherapy-based
protocols
|
Bendamustine Plus
Rituxan PMID:
15908650
Patient's story-
Bendamustine overcomes refractory nhl
|
Bendamustine
Topic
Search
A recent study of the drug bendamustine shows it
gives patients with advanced lymphoma
an option when other
treatments fail. According to Oncologist Jonathan Friedberg,
M.D.
of the University of Rochester, 70 percent of the patients in a
trial study had
good responses to the treatment. He says 35
percent even went into remission. |
|
|
Fludarabine Related
abstracts | Topic
Search |
|
Metronomic
chemotherapy (low/continuous dosing). Topic
Search
|
oral low-dose PEP-C
PAL |
|
|
Phase II study of paclitaxel
and estramustine in patients with recurrent and refractory NHL
Cancer. 2004 Sep 28 PMID:
15455357 |
|
Bortezomib (Velcade) With Standard Chemotherapy for Relapsed or
Refractory
Follicular Lymphoma ClinicalTrials.gov
The purpose of this study is to evaluate the effectiveness and
safety of combining bortezomib (Velcade) with rituximab,
fludarabine, mitoxantrone, and dexamethasone in treating patients
with follicular cell lymphoma. |
|
Novel / targeted
therapies
See also Pipeline
|
Radioimmunotherapy
|
Radioimmunotherapy
(Bexxar or Zevalin)
|
Return to top
Hodgkin's Lymphoma - Refractory
/ Relapsed
Treatment
Search for relapsed HL PubMed
| ASCO.org Clinical
Trial Search for relapsed HL ClinicalTrials.gov
|
Stem Cell Transplantation (SCT)
|
|
Targeted
/ Novel therapies
See
also Pipeline
|
Bispecific antibodies
- (early investigational) novel investigative
treatment for refractory Hodgkin's
disease - PubMed |
|
Cytotoxic
T lymphocyte therapy for Epstein-Barr virus+ Hodgkin's
disease PubMed |
|
*
|
|
Genetic
modification of tumor-antigen presenting cells and
T-lymphocyte transfer PubMed |
|
Rituxan
in lymphocyte predominance Hodgkin's disease: a case series PubMed |
|
|
Chemotherapy-based
|
PEND Chemotherapy in
Patients with Refractory/Relapsed Hodgkin Lymphoma.
Leuk Lymphoma. 2004;45(10):2079-2084. PMID:
15370253 | Related
articles |
|
Ifosfamide,
Carboplatin and Etoposide (ICE)
chemotherapy in transplant-eligible patients with non-Hodgkin's
lymphoma and Hodgkin's disease. Ann Oncol. 2003;14 Suppl 1:i11-6. PMID:
12736225 |
|
Gemcitabine,
Dexamethasoneare and Cisplatin is an active and non-toxic
chemotherapy regimen in relapsed or refractory Hodgkin's disease:
a phase II study by the National Cancer Institute of Canada
Clinical Trials Group. Ann Oncol. 2003 Dec;14(12):1762-7. PMID:
14630682
|
|
NOVP:
a novel chemotherapeutic regimen with minimal toxicity for
treatment of Hodgkin's disease PubMed |
|
|
Radiotherapy
|
Radiotherapy
Topic Search |
|
Phase
I study of escalating doses of low-dose-rate, Loco-regional
irradiation preceding Cytoxan-TBI (Total Body
Irradiation) for patients with chemotherapy-resistant
non-Hodgkin's or Hodgkin's lymphoma.
Int J Radiat Oncol Biol Phys. 2003 Sep 1;57(1):166-71. PMID:
12909229 |
|
Return to top
Also
see NHL - unspecified | PubMed
| ClinicalTrials.gov
Treatment
Search for relapsed MCL PubMed
| ASCO.org Clinical
Trial Search for relapsed MCL ClinicalTrials.gov
Stem Cell
transplants (SCT)
|
Topic
Search |
|
Tandem Transplants: Patients with mantle-cell
lymphoma relapsing after autologous
stem cell transplantation may
be rescued by allogeneic transplantation. Bone Marrow Transplant.
2000 Sep;26(6):677-9. PMID: 11035375 |
Allogeneic SCT
Autologous SCT
|
Topic
Search | PubMed
abstracts | PAL |
|
Bexxar,
High Dose with SCT High-Dose Iodine-131-Labeled Rituxan
and Autologous Stem
Cell Support Produces Long Lasting Effects in
Patients with Mantle Cell Lymphoma Failing
Conventional Autologous
Transplants cancerconsultants.com |
Chemotherapy-based
protocols for relapsed MCL
|
Bendamustine Plus
Rituxan in Mantle Cell and Low-Grade Non-Hodgkin's Lymphoma.
J Clin Oncol. 2005 May 20;23(15):3383-9. PMID:
15908650 |
|
Gemcitabine and
Oxaliplatinum an effective regimen in a patient with
progressive refractory
MCL Leuk Lymphoma. 2004
Jun;45(6):1289-91. PMID:
15360015 | Related
articles |
|
High (95%) Response
Rates in Relapsed/Refractory Mantle Cell Lymphoma after R-HCVAD
Alternating with R-Methotrexate/Cytarabine (R-M-A). Session
Type: Poster Session 650-II ASH
2005 |
Targeted / Novel
Therapies
Treatment
Search Web
See also Pipeline
|
BMS 247550
ASCO
2005 | Clinical
trial | Topic
Search
The
epothilones are a new class of natural products. |
| CCI-779 Single-agent CCI-779 has substantial anti-tumor activity in relapsed MCL. This study
demonstrates that agents, which selectively target cellular pathways dysregulated in MCL cells
can produce therapeutic benefit. The high response rate warrants further studies of this agent in MCL,
but the high incidence of hematologic toxicity suggests that a lower dose should be explored.
CCI-779 at 25mg is currently being evaluated in MCL through an NCCTG trial
Abstract #129
appears in Blood, Volume 104, issue 11, November 16, 2004
Also see: Clinical
Trial |
|
*
|
|
Maintenance
therapy with Rituxan PMID:
16946304 |
|
Radioimmunotherapy
for MCL
|
Topic
Search | PAL |
|
Zevalin® for
Treatment of Patients with Relapsed and Refractory MCL.
Session Type: Poster Session 845-II ASH
2004 |
|
|
Revlimid
(lenalidomide)
|
|
Targeting
Angiogenesis in Mantle Cell Lymphoma
|
|
Velcade (Bortezomib)
|
Return to top
Marginal Zone (MZL) / MALT - Richter's - Refractory /
Transformed
Treatment
Search for relapsed MZL PubMed
| ASCO.org
Treatment
Search for Richter's (transformed) MZLPubMed
| ASCO.org
Also
see NHL - unspecified | PubMed
| | |
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