|
NOVEMBER 1999
BREAST CANCER
Recombinant human
anti-HER2 monoclonal antibody (rhuMAb HER2). Melody Cobleigh and colleagues
conducted a multicenter trial in 222 women with HER2-overexpressing
metastatic breast cancer in which patients were treated with single agent
rhuMAb HER2 (Herceptin; Genentech, Inc.) after the cancer had failed to
respond to 1 or 2 chemotherapy regimens. The intent-to-treat analysis revealed
a 15% response rate (8 CRs, 26 PRs), a median time to disease progression of
3.1 months (0 to > 28 months), and a median survival time of 13 months
(0.5 to > 30 months). For responders, the median duration of response was
9.1 months (1.6 to > 2.6 months). The most clinically important adverse
event was cardiac dysfunction (4.7% of patients) and the most common adverse
events were infusion-related fever/chills (40% of patients). These results
show that rhuMAb HER2 is well tolerated and active as a single agent in
patients with HER2-overexpressing progressive metastatic breast cancer.
(Cobleigh MA, et al. J Clin Oncol 1999; 17: 2639-2648)
OVARIAN CANCER
Photoimmunotherapy
(PIT) and cisplatin. PIT consists of the antibody-targeted delivery of a photosensitizer
that is activated to a cytotoxic state by visible light and, when applied
intraperitoneally, represents a potentially new therapeutic option for
advanced ovarian cancer patients. Linda Duska et al. performed a preclinical
study comparing the cytotoxic effects of the combination of PIT (utilizing a
monoclonal antibody directed against CA 125) and cisplatin to cisplatin
treatment alone in several human primary and established ovarian cancer cell
lines. They observed cytotoxicity to be an average of 6.9 x greater with the
combination compared to cisplatin therapy alone (P=0.023). In addition, the
combination resulted in a higher increase of cytotoxicity for
cisplatin-resistant cells than for cisplatin-sensitive cells (P=0.042). These
data indicate that PIT may augment cisplatin therapy and possibly reverse
cisplatin-resistance in human ovarian cancer cells. (Duska LR, et al. J Natl
Cancer Inst 1999; 91: 1557-1563)
HEMATOLOGIC
MALIGNANCIES
Interferon (IFN) and
multiple myeloma. Martin
Oken and colleagues report the results of an ECOG study in which previously
untreated patients with active multiple myeloma (628 evaluable patients) were
randomized to VBMCP chemotherapy alone, VBMCP + rIFNa2 (Schering-Plough) or
VBMCP + high dose cyclophosphamide (only in patients < 70 years old).
While subanalyses indicated that IFN therapy may add benefit (greater CR rate
and longer response duration) to elderly patients and those with IgA myeloma,
there were no differences between the 3 regimens in rates of response or survival.
The results of this large trial show that the addition of IFN to VBMCP
chemotherapy does not affect survival rates or overall response rates in
previously untreated patients with multiple myeloma. (Oken MM, et al. Cancer
1999; 86: 957-968)
Rituximab associated
cytokine release syndrome. U. Winkler and coworkers describe a cytokine-release
syndrome that developed during the initial rituximab (IDEC Pharmaceuticals)
infusion in 6 of 11 patients (10 B-CLL and 1 leukemic variant of mantle cell
lymphoma) who presented with high peripheral blood malignant lymphocyte
counts (> 50 x 109/L). In all six patients, lymphocyte counts decreased
rapidly and elevated serum TNF-a and IL-6 levels were found. The syndrome is
manifested by severe symptoms (fever, chills, nausea, vomiting, hypotension,
dyspnea), thrombocytopenia, prolongation of the prothrombin time, and large
increases of serum LDH and liver enzyme levels. These findings indicate that,
in patients with high numbers of circulating malignant lymphocytes, alternative
methods to lower the tumor burden (e.g, hydroxyurea or a fractionated
rituximab schedule) are needed prior to the initiation of standard rituximab
treatment. (Winkler U, et al. Blood 1999; 94: 2217-2224)
Interferon (IFN) effects in chronic myeloid leukemia
(CML). Fabrizio
Pane et al. measured levels of hybrid BCR/ABL mRNA in bone marrow mononuclear
cells (MNCs) by reverse transcriptase-PCR from 20 patients with Philadelphia
positive (Ph+) CML before and after therapy with IFN-a or hydroxyurea (used
in IFN-a resistant CML). At the time of hematologic remission, the mean
levels of BCR/ABL transcripts in marrow MNCs were reduced in those with IFN
sensitive disease (P<0.001) but not in those with IFN resistant disease.
Similar results were seen in cell culture experiments. These results suggest
that downmodulation of BCR/ABL gene expression may be a mechanism of action
of IFN-a in CML. (Pane F, et al. Blood 1999; 94: 2200-2207)
|