Combination therapies chemotherapy

The benzodiazepine, lorazepam, acts allosterically on GABAa receptors to facilitate the actions of GABA. Lorazepam has some antiemetic activity in cancer chemotherapy. When used in combination therapy, it does not appear to add to antiemetic control but may contribute to a reduction in anxiety. 

Indicahons for combined therapy are now considered to be much fewer than originahy thought. There is also the problem of a chemical or physical incompahbility between two dmgs. Examples where combinahons have an important role to play in anhbacterial chemotherapy were provided earlier (sections 2.3 and 2.9) in which a fi-lactamase inhibitor and an appropriate j3-lactamase-labile penicillin form a single... 

Radiation therapy is the treatment of choice for chemotherapy-resistant tumors such as non-small cell lung cancer (NSCLC) or in chemotherapy-refractory patients with SVCS. Between 70% and 90% of patients will experience relief of symptoms. Radiation therapy also may be combined with chemotherapy for chemotherapy-sensitive tumors such as SCLC and lymphoma. In the rare emergency situations of airway obstruction or elevated intracranial pressure, empirical radiotherapy prior to tissue diagnosis should be used. In most patients, symptoms resolve within 1 to 3 weeks. 

The management of complex nausea and vomiting, for example, in patients who are receiving cytotoxic chemotherapy, may require combination therapy. 

SCLC is very radiosensitive. Radiotherapy has been combined with chemotherapy to treat limited disease SCLC. This combined-modality therapy prevents local tumor recurrences but only modestly improves survival over chemotherapy alone. 

Treatment options include radiation therapy, chemotherapy, or both (combined-modality therapy). The therapeutic role of surgery is limited, regardless of stage. 

Rituximab, a chimeric monoclonal antibody directed at the CD20 molecule on B cells, has become one of the most widely used therapies for follicular lymphoma. Rituximab is approved for first-line therapy either alone or combined with chemotherapy and as maintenance therapy for patients with stable disease or with partial or complete response following induction chemotherapy. 

Malignant mesothelioma, described more than 100 years ago, is a comparatively rare tumor that occurs in the pleura and peritoneum, membranes that surround the lungs, line the thoracic cavity, surround the gut, and line the abdominal cavity. The survival time of mesothelioma patients is often less than a year, in spite of chemotherapy and radiotherapy. Combined therapy and surgical resection in cases of early diagnosis, a treatment currently being tested, has produced a few long-term (more than five years) survivors (Ant-man, et ah, 1980 Antman et ah, 1983), usually in cases with peritoneal rather than pleural involvement. 

Raju PI, Maruyama Y, DeSimone P, et al. Treatment of liver metastases with a combination of chemotherapy and hyperfractionated external radiation therapy. Am J Clin Oncol 1987 10 41-43. 

Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 1988 80 751-755. 

Within the multiple subsites of this tumor grouping, most work has been done in esophageal cancer. The large majority of these patients have been treated with paclitaxel in combination with radiation (Table 3). The experience with docetaxel is essentially limited to patients treated on phase I trials for thoracic malignancies that used radiation in combination with docetaxel (68,111). The situation is much the same for both pancreatic and gastric cancers as well. The rationale for looking at combination therapy that incorporates paclitaxel is much the same as in other disease sites, i.e., its activity in systemic disease (112), its potent preclinical radiosensitizing properties (38), and evidence from randomized trials that there is a benefit to combined modality therapy that includes at least radiation and chemotherapy (113-116). 

Hyperfractionated radiation decreases the fraction size but is repeated hours later. So, the overall days of treatment are decreased. The total dose is maintained similar to once-daily (conventional) radiation or a slightly higher dose is given. Theoretically, twice-daily radiation therapy decreases the repopulation of tumor cells. Choi established the maximum tolerated dose of hyperfractionated radiation therapy given twice-daily as 45 Gy in 30 fractions over three weeks and the maximum tolerated conventional dose was 70 Gy in 35 fractions over 7 wk (3/). Several phase II studies demonstrated the efficacy of hyperfractionated radiation therapy combined with chemotherapy (31-34). 

The theory is that the earlier the combination is administered the better the chance for the resistance to be overcome. Unfortunately, cross-resistance can occur (9,43,44). Several randomized studies have demonstrated that the combination of chemotherapy and radiation therapy improves overall survival compared to chemotherapy alone (Table 1 and 1A). 

The optimal timing and sequence of combining chemotherapy and radiation therapy is unknown for the treatment of limited-stage small-cell lung cancer. Radiation can be combined with chemotherapy sequentially, alternating, or concurrently. When combined concurrently, radiation can be started early in the treatment or later during the treatment schedule. 

Sequential combinations complete chemotherapy first and then follow it with radiation therapy. The advantages of this schedule are decreased toxicity and increased ability to deliver full doses of chemotherapy. The disadvantage is that there is an increased chance of developing therapy-resistant tumors (36). 

Additionally, MMPIs are not expected to replace currently used, proven-effective modalities of cancer treatment such as radiotherapy, hormonal/chemotherapy, or surgery. It is predicted that they will be clinically developed for use in combination with these agents. As expected, given nonoverlapping toxicities and differing mechanisms of action, MMPIs have been combined preclinically with radiation therapy (4), cytotoxic (5-9), resultant additive or supraadditive efficacy. With these data in mind, the ability to combine an MMPI with radiation therapy, chemotherapy, and hormonal therapy may become an important feature in the ultimate clinical success of these agents. 

For some indications combination chemotherapy is indicated however then bacteriostatic or bactericidal agents should not be mixed. Synergism between the actions of different drugs is one of the aims of combination therapy. Other indications are delay of development of resistance or the treatment of mixed infections. 

A systematic review in the Cochrane database of forty-nine trials of chemotherapy for advanced ovarian cancer involving 8763 women concluded The available evidence, although not conclusive, suggests that platinum-based chemotherapy is better than non-platinum therapy. There is some evidence that combination therapy improves survival compared with platinum alone. No difference in effect has been shown between cisplatin and carboplatin (see Advanced Ovarian Cancer Trialists Group, 1999). 

The chemotherapy of advanced Hodgkin s disease is one of the best examples of successful combination chemotherapy. Combination therapy with the MOPP regimen (mechlorethamine, Oncovin [vincristine sulfate], procarbazine, prednisone), alternating with ABVD (Adriamycin [doxorubicin hydrochloride], bleomycin, vinblastine, dacarbazine), has resulted in cure rates of 50 to 60%. 

G. Other applications According to Micromedex, further potential roles for Rituxan include combination with chemotherapy in low-grade or intermediate-grade disease, first-line therapy of B-cell lymphoma, and use in other malignancies with CD20-antigen expression (e.g., chronic lymphocytic leukemia).Treat-... 

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