Indolent NHL is a slow-growing form of lymphoma. It encompasses what had been called low-grade NHL and some categories of intermediate-grade NHL. Depending on the type of cancer, patients today often live years without a lot of treatment. The usual strategy had been to wait until symptoms were manifested to a large degree before treatment was ordered.
However, with newer immunotherapies now available, the era of watching and waiting may be over, because effective treatment may begin as soon as the lymphoma is detected.
Immunotherapies include rituximab; alemtuzumab (Cam-path, Genzyme); and the conjugated monoclonal antibodies ibritumomab tiuxetan (Zevalin, Biogen Idec) and 131-I tositu-momab (Bexxar, GlaxoSmithKline). These last two agents are linked to a radioactive isotope to target and kill specific cancer cells. canadian pharmacy viagra
Rituximab Combinations. In a large study by the European Organization for Research and Treatment of Cancer (EORTC), rituximab maintenance therapy improved progression-free and overall survival in patients with relapsed or refractory follicular lymphoma following induction with CHOP or R-CHOP when compared with placebo maintenance. The investigators concluded that R-CHOP and R-fludarabine phosphate (Fludara, Berlex) combinations were superior to ritux-imab alone or rituximab plus R-CVP in producing complete remissions. In addition, rituximab/fludarabine combinations produced complete remissions in 85% of patients; by contrast, R-CHOP led to complete remissions in 65% of patients.
Researchers from the M.D. Anderson Cancer Center in Houston, Texas, reported that the addition of rituximab to CHOP provided a high response rate and excellent early survival in a group of 45 patients with newly diagnosed follic-ular lymphoma who were considered to have a good prognosis. These patients had a complete response rate of 96%. With a median follow-up of 33 months, a three-year failure-free survival of 73% was reported, with an overall survival of 97%.
Cytotoxic Agents. Newer cytotoxic agents for follicular lymphoma include:
- bendamustine HCl (Treanda, Cephalon) (alkylating and nucleoside analogue moieties).
- proteasome inhibitors (Millennium; A. G. Scientific).
- bortezomib (Velcade, Millennium) alone or in combination with rituximab.
- targets of apoptosis.
- antisense (Genasense).
- pan-Bcl-2 inhibitors (obatoclax mesylate, GX15-070MS, Boehringer Mannheim).
- BH3 (Bcl-2 homology 3) domain-only small molecules and cell death receptors (tumor necrosis factor-related apoptosis-inducing ligand [TRAIL monoclonal antibody]).
- calicheamicin, a natural product derived from Micro-monospora echinospora.
- gemtuzumab ozogamicin (Mylotarg, Wyeth), an anti-leukemia drug based on calicheamicin.
- inotuzumab ozogamicin (CMC-544, Wyeth), a compound similar to calicheamicin.
Immune-Based Agents. Other immune-based therapies include:
- anti-idiotype vaccines (tumor-derived immunoglobulin idiotype antigen vaccines, National Cancer Institute).
- cell-based vaccines (autologous tumor cells plus GM-CD40L plus low-dose interleukin-2).
- pulsed dendritic cells (Life Technologies, Inc.; Boehringer Mannheim)
Bendamustine does not interfere with other commonly used chemotherapy alkylating agents. It has been used in Germany for many years for the treatment NHL, CLL, multiple myeloma, breast cancer, and other solid tumors such as lung cancer. When bendamustine was administered to patients who had stopped responding to prior therapy, 74% experienced an anti-cancer response and more than one-third (39%) experienced a complete disappearance of detectable cancer.
The outcome in patients with follicular lymphoma has changed, showing clear benefits in progression-free survival and overall survival, as with the use of monoclonal antibodies along with chemotherapy. The long-term impact is still unclear, but this is the first time that such treatment demonstrated improvement in overall survival in follicular lymphoma.