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BioOncology Watch Timely Information for Practicing
Physicians |
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AUGUST 2000 Non-Hodgkin’s Lymphoma (NHL) First-line therapy of low-grade NHL with rituximab. John Hainsworth and colleagues report the
findings of a phase II study of rituximab therapy for previously untreated
patients with low-grade NHL.
Rituximab was given intravenously at a dose of 375 mg/m2/weekly
x 4. Patients with objective
responses or stable disease after the initial month of treatments were to
receive additional 4-week courses of rituximab at 6-month intervals for 2
years. At the time of the report 39
patients had completed the first course of rituximab treatment. Twenty-one patients (54%) had a response
(2 CRs), 14 patients (36%) had stable disease, and 4 patients had disease
progression. During the first 6
months of follow-up only 2 patients progressed while 3 PR and 2 stable disease
patients converted to CRs and PRs, respectively. Thirteen patients have undergone a second course of rituximab
therapy during which response improvement occurred in 3 patients and disease
progression occurred in 1 patient.
Thirty-two of 39 patients were free of disease with a median follow-up
of 8 months. Only 1 patient has
experienced a grade 3/4 infusion-related toxicity (flushing associated with
dyspnea and chest pain). The data
from this small trial suggest that rituximab is a safe, active first-line
agent in NHL. The data also indicate
that the response rate of NHL patients for first-line rituximab treatment is
similar to that of rituximab used in the second-line setting. In addition, the value of dose
intensification in rituximab studies has been unclear and further follow-up
in this study is needed to define the role for repeated pulse dosing of
rituximab. (Hainsworth JD, et al. Blood
2000;95:3052-3056) Interferon alfa consolidation. Richard Fisher and coworkers report that results of a phase III
Southwest Oncology Group study (S8809) in which patients with previously
untreated stage III or IV low-grade NHL were registered to receive 6-8 cycles
of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, and
mechlorethamine, vincristine, procarbazine, prednisone (ProMACE [day 1] –
MOPP [day 8]) chemotherapy with or without radiotherapy (n=571). Subsequently, 268 responding patients were
randomized to interferon alfa consolidation (interferon alfa-2b 2 mU/m2
subcutaneously 3x weekly for 2 years) (n=144) or to observation alone
(n=124). Overall survival at 5 years
was 78% for the interferon group compared to 77% for the observation group
(p=.65). The median progression-free
survival time was 4.1 years for the interferon-treated patients and 3.2 years
for the control patients (p=.25).
These results show that interferon alfa consolidation therapy
following chemotherapy did not prolong overall or progression-free survival
for these low-grade NHL patients.
(Fisher RJ, et al. J Clin
Oncol 2000;18:2010-2016) High-Risk Melanoma
Adjuvant interferon alfa-2b (IFN a2b). Adjuvant therapy with high-dose IFN a2b (HDI)
(Schering Plough Corp.) administered for 1 year to high-risk (stage IIB and
III) melanoma patients (pivotal trial E1684) has been shown to prolong
relapse-free and overall survival (RFS and OS). However, HDI is associated with substantial toxicity. Thus, John Kirkwood et al. evaluated
low-dose IFN a2b (LDI;
3 megaunits/day subcutaneously 3x weekly) for 2 years versus HDI (20 megaunits/m2/day
intravenously 5 days per week for 4 weeks; then 10 megaunits/m2/day
subcutaneously 3x weekly) for 1 year versus observation alone as adjuvant
therapy for patients with stage IIB or stage III melanoma in a large (n=642)
intergroup study (E1690). At a median
of 52 months of follow-up, no differences in OS were observed between the 3
treatment arms. The estimated 5-year
RFS rates were 44%, 40%, and 35% for the HDI, LDI, and observation arms,
respectively. In a Cox model analysis
adjusting for significant prognostic variables, the impact of HDI, but not
LDI, on RFS achieved significance (p=.03).
The results of this trial indicate the HDI, but not LDI, has a RFS
benefit for high-risk melanoma patients.
However, OS was similar between the HDI- and LDI-treated
patients. The authors speculated that
a survival difference favoring IFN a2b-treated patients was not seen in this trial (E1690) in
contrast to study E1684 because a larger proportion of patients in the
observation arm of E1690 received IFN a2b salvage therapy (31% vs. 15%). The median OS of patients in the E1690
observation group was 6 years compared to 2.8 years for patients in the E1684
observation group. (Kirkwood JM, et
al. J Clin Oncol 2000;18:2444-2458) Prostate Cancer
Antigen-specific cellular immunity.
Animal studies indicate that dendritic cells exposed to
prostatic acid phosphatase (PAP) induce anti-PAP cellular immunity and that
subcutaneous injections of PAP as a soluble antigen induce an antibody
response (humoral immunity). Thus,
Patrick Burch and colleagues conducted a phase I trial in which 13 patients
with advanced hormone refractory prostate cancer were treated with 2 monthly
intravenous infusions of autologous dendritic cells (APC8015; Dendreon Corp.)
that had been pre-exposed to PA2024 (a fusion protein consisting of human
granulocyte/macrophage colony stimulating factor and human PAP) following by
3 monthly subcutaneous injections of PA2024 at 0.3, 0.6, or 1.0
mg/injection. The treatments were
tolerated well, prostate-specific antigen (PSA) levels were decreased in 3
patients, and T cells from all patients evaluated (n=9) proliferated in vitro
in response to PA2024. All evaluable
patients (n=11) also developed antibodies to PA2024, however only 2 patients
developed titers >40 and only 5 patients developed antibodies specifically
to PAP. In contrast, 15 to 31
patients who had received only APC8015 in a previous study developed antibody
titers >40 to PA2024. These data
show that dendritic cells exposed to antigen ex vivo can induce antigen-specific cellular immunity and suggest
that injection of PA2024 suppressed antibody generation compared to
administration of APC8015 alone.
(Burch PA, et al. Clinical
Cancer Res 2000;6:2175-2182) |
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