Overall response rate

Interestingly, all these monoclonal antibodies have a poor antitumor activity when used as single agents, with overall response rates of about 10%. Thereby, these monoclonal antibodies have all been approved in combination with classical cytotoxic agents or radiation therapy. 

Ovarian ablation (oophorectomy) is considered by some to be the endocrine therapy of choice in premenopausal women and produces similar overall response rates as tamoxifen. Medical castration with an LHRH analog, goserelin, leuprolide, or triptorelin, is a reversible alternative to surgery. 

The most frequently used regimen is cisplatin or carboplatin combined with etoposide. Irinotecan in combination with cisplatin has also been shown to be active (see Table 63-1). Overall response rates and survival durations are generally superior for patients with limited stage versus those with extensive stage disease. 

Multicentre studies have demonstrated the efficacy of rituximab, a chimeric IgG-1 directed against CD20, in the treatment of relapsed low-grade and follicular non-Hodgkin lymphoma. In 166 patients, receiving 375 mg rituximab in four weekly doses, the overall response rate was 50% in 161 evaluable patients who had previously received chemotherapy... 

There is certainly less data available on the role of concurrent docetaxel with radiation in the treatment of locally advanced nonsmall-cell lung cancer. Koukourakis et al. (66) have reported on their phase I/II experience of administering radiation concurrently with docetaxel for stage IIIB NSCLC. In the phase II portion of their study, 30 mg/m2 of docetaxel was given weekly with concurrent 64 Gy of thoracic radiation. Esophagitis was the main side effect of the regimen wherein 17% of patients needed a two-week treatment delay and another 31 % of patients required minor delays (3-7 d). Thirty-five patients were enrolled and evaluable, and the overall response rate was 80% (34% CR). The median survival was 12 mo, and 1-yr survival rate was reported as being 48%. 

Single-agent activity of paclitaxel was initially evaluated by the Eastern Cooperative Oncology Group (ECOG) in a select cohort of 34 patients with unresectable, recurrent, or metastatic disease (34). The overall response rate was 40% (4 CR, 8 PR). Myelosuppression was the primary toxicity. The median survival was 9.2 mo with a 1-yr survival of 33%. 

Combination regimens utilizing standard chemotherapy as a single modality have been attempted with increased toxicities reported but impressive overall and complete response rates as high as 27% for patients with recurrent and metastatic disease (74). Schrijvers and colleagues concluded that the addition of interferon a-2b (IFN-a) as a biomodulator of 5-FU and cisplatin in the recurrent or metastatic setting offered no benefit (75). One hundred twenty-two patients were randomized to cisplatin (100 mg/m2, d 1) and continuous infusion 5-FU (1000 mg/m2, d 1-4) with or without the addition of IFN-a. The overall response rates (47.1% vs 38.4%, p > 0.50) and median survival (6.3 vs 6 mo, p = 0.49) with and without the addition of INF-a, respectively were similar in both arms and were not statistically significant. 

Despite G-CSF support, neutropenia was frequently encountered (70% in arm A, 78% arm B). Thirty-one percent of patients failed to complete their recommended treatment due to toxicity or patient refusal. Overall response rates in both arms were comparable (35% high-dose combination vs 36% low-dose combination) and were determined to be suboptimal not warranting further investigation. 

Phase II studies of paclitaxel, infused as a single agent over 24 h every 3 wk, showed promising results for patients with metastatic or locally unresectable esophageal cancer. The overall response rate was 32%, with a median survival of 13.2 mo (53). 

In addition, Safran et al. (13) presented preliminary data on preoperative chemoradiotherapy using paclitaxel (Taxol) inpatients having T2-T4 N0-N3 adenocarcinoma. They found an overall response rate of 63% with acceptable toxicity. 

Sustained viral response rates substantially better when combined with ribavirin (genotype 1 40%-50% genotype 2 or 3 70%-80% for combination therapy overall response rate 40% for monotherapy)... 

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