<Oncology Frontier>:Induction chemotherapy is also known as primary， preoperative， basal and neoadjuvant chemotherapy. In which kind of situation will a patient need induction chemotherapy?

　　《肿瘤瞭望》: 诱导化疗又被称作一线治疗、术前治疗、基础治疗和新辅助治疗，在什么情况下，患者需要进行诱导化疗？

　　Dr Taguchi: Previously， surgery was followed by chemotherapy and post-operative chemotherapy used to be the standard but not necessarily effective. There was only a small difference between the efficacy of surgery alone and surgery plus chemotherapy. When given pre-operative chemotherapy (or induction or primary chemotherapy) for locally advanced cancers without distant metastases (such as liver and lung)， results were so much better. When doing the trials on cancer chemotherapy， we included mostly patients with advanced cancers and the results were not so encouraging， but when we tried pre-operative chemotherapy with localized advanced cancers， we were surprised at the success， sometimes producing complete remission. From the consequent comparative controlled trials， pre-operative chemotherapy proved to be much more effective than post-operative in terms of response rate and disease-free survival.

　　《肿瘤瞭望》:  诱导化疗有两种方式，经导管诱导和全身诱导，如何选择这两种方案？

　　Dr Taguchi: I was a surgeon initially， not a medical oncologist. The use of chemotherapy for solid tumors was started by surgeons when surgery was the standard therapy for such cancers. But many times surgery was not enough on its own. I was the first person in Japan to try intra-arterial infusion. Because tumors get their blood supply via the arteries， by infusing anticancer drugs directly into the artery， we could target the tumor specifically and effectively. In advanced cases with metastases however， we cannot use this technique， as it is only a localized or regional treatment. It is also a very technical procedure and can be difficult to achieve. But I have reported here at the meeting that a 20-30% higher response rate can be achieved. If the tumor is localized and only one artery supplies the tumor， intra-arterial infusion is very effective. In more advanced cases however， it is less effective and more difficult to perform， so many physicians will not use it. Today， anticancer drugs have advanced so far and are so effective that is better to use modern regimens even if used systemically. So the intra-arterial technique is losing popularity， despite its earlier successes.

　　田口铁男教授:最初我仅是一名外科医生，不是肿瘤学专家。实体瘤的化疗是由外科医生提出的，当时手术切除是肿瘤的标准治疗。很多情况下，仅手术是远远不够。我是日本第一个尝试动脉灌注的人。肿瘤通过动脉获得血液供应，动脉灌注抗肿瘤药物则能够特异、有效抗肿瘤。然而在有远处转移的患者中，并不能采用这种技术，因为它仅是区域或局部治疗方法，这项技术操作也很难实现。在会议上，我在报告中指出20%～30%患者有较高的缓解率。如果肿瘤非常局限，并且只有一条动脉供应血液，那么动脉灌注将非常有效。然而在进展期肿瘤中，疗效较差且很难实现。因此，很多医师不采用此方法。目前抗肿瘤药物发展如此迅速，并且非常有效，我们还是倾向使用现代的治疗方案，甚至是全身治疗。这也是为什么动脉化疗在早期很成功，现在不受欢迎的原因。

　　<Oncology Frontier>:Stop-and-go strategies especially fit with therapies inducing cumulative toxicity， such as with oxaliplatin. At the time of disease progression during the oxaliplatin off period， how do we best predict the efficacy of oxaliplatin reintroduction?

　　《肿瘤瞭望》: 晚期结直肠癌一线治疗有“stop and go”的策略来减轻某些化疗药的累积毒性，例如奥沙利铂的神经毒性。当停用OXA后出现病情进展，如何预测再次启用OXA是否还能获得疗效？

　　Dr Taguchi: Oxaliplatin is a platinum compound with very strong antitumor activities and also very toxic， so it is important how often and how much you use. Cisplatin and oxaliplatin are usually used at three- or four-week intervals. After a single injection， by two weeks leucopenia occurs which recovers by week three， so a cycle of three to four weeks is required. Sometimes the total dose can be divided over a week and given on day 1， 3， 5 and 7 for a total of 100mg/m2 MTD for cisplatin. The maximum tolerated dose (MTD) for oxaliplatin is 130mg/m2. Side effects need to be carefully considered. They can be used in combination with antimetabolites like 5-FU more often， for example， every week or between day 1 and 5 and then rested for two to three weeks.

　　田口铁男教授: 奥沙利铂是铂类化合物，有很强的抗肿瘤活性，毒性也比较大，因此使用频率和剂量是非常关键的。奥沙利铂和顺铂均为三周或四周使用一次。单药注射铂后两周后，出现白细胞减少，三周后恢复正常，因此三周或四周一个疗程均可。有时也可以在一周内分开给予，在第1、3、5、7天给药。顺铂的最大耐受量是100 mg/m2 ，奥沙利铂的最大耐受量（MTD）是130 mg/m2。不良反应也需要慎重考虑。它们也常常与抗代谢药物如5-FU联合使用，例如，一周一次或者在第1、5天给药，然后休息2～3周。

　　<Oncology Frontier>:What’s the best timing for surgery for a patient who has undergone induction chemotherapy?

　　《肿瘤瞭望》:  在进行诱导化疗后，如何选择手术时机？

　　Dr Taguchi: Of course， when there has been a complete response and when any leucopenia has recovered. Usually， induction chemotherapy involving an anthracycline-based regimen， like doxorubicin plus 5-FU or taxane is repeated over three or four cycles over three months， and then a recovery period until leucopenia， thrombocytopenia and other side effects have rebounded and then surgery is performed. Sometimes we have to check for a clinical complete response (CR) and pathological complete response (pCR). When tumors completely disappear， it is referred to as a clinical complete response or remission. When after surgery， the tumor could not be completely removed， that would be an incomplete pathological response. It is often difficult to achieve a clinical complete response. When induction chemotherapy was first introduced， for locally advanced cases of cancer (stage two or three)， we were doing surgery first. More recently， we do pre-operative chemotherapy first and can achieve a complete response or tumor shrinkage， which makes the operation easier.

　　田口铁男教授: 当然是在达到完全缓解、白细胞恢复正常后。通常情况下诱导化疗以蒽环类药物为治疗方案，如多柔比星联合5-FU或紫杉醇，三、四周期或三个月后；白细胞减少、血小板减少和其他副作用均恢复后，给与手术治疗。有时我们需要检查是否达到完全缓解（CR）、病理学完全缓解（pCR）。当肿瘤完全消失时，我们称为临床完全缓解或者缓解。如果手术没有全部切除肿瘤，就没有达到完全病理缓解，也很难达到临床完全缓解。在第一次提出诱导化疗之前，癌症局部晚期（II期、III期）的患者，我们先进行手术治疗。现在，我们先进行新辅助化疗达到完全缓解或使肿瘤缩小，手术也变得更加容易。

　　<Oncology Frontier>:As the first President of the Asian Clinical Oncology Society (ACOS)， what is your expectation for the future of ACOS?

　　《肿瘤瞭望》:  作为ACOS的首届主席，请您展望一下亚洲临床肿瘤协会（ACOS）的发展方向。

　　Dr Taguchi: At that time in 1991， I was President of the Japanese Clinical Oncology Society and invited more than forty doctors from ten Asian countries as well as Europe and the US. It was a big congress. We had discussions amongst the delegates from the Asian countries and decided to start an Asian Clinical Oncology Society because cancers have quite different natures and characteristics in Asian populations and in some cases anticancer drugs work better in Asians than in Caucasian patients. Metabolism is also quite different. For example， 5-FU derivatives are more effective in Asian patients and are too toxic in Caucasians. Why? Oral forms of 5-FU are metabolized more slowly in Asians and are gradually transformed to 5-FU so toxicity is low. But in Caucasians， the conversion to 5-FU is very rapid so circulating concentrations go up very quickly causing toxicity. For the oral forms of 5-FU， the Japanese MTD is 40mg/m2 but is 25mg/m2 in Caucasians. Because of these differences， it was important to have a Society specific to Asia and even between countries， health systems are different. It is still a big problem. Between Japan， Korea and China， we have many old and traditional treatments as well， compared to the more advanced therapies of Europe and the United States.

　　田口铁男教授:1991年，我是日本临床肿瘤学主席，邀请了来自亚洲十国、欧洲及美国的40多位医生。这是一个很大的会议，我们亚洲代表进行了讨论，决定成立亚洲临床肿瘤学会。因为癌症在亚洲人群中有不同的性质和特点。有时候，抗肿瘤药物在亚洲人中比白种人更有效。同时，代谢也不同。例如，5-FU衍生物在亚洲人中更有效，但是在白种人中毒性更大。为什么呢?口服5-FU在亚洲人中代谢较慢，是逐渐转化为5-FU，因此毒性较小。但是在白种人中，5-FU转化很快，血液循环中的5-FU浓度上升很快，引起毒性。日本人口服5-FU的MTD是40 mg/m2，而白种人则为25 mg/m2。由于这些差异，在亚洲甚至国家间需要有一个特定的学会。医疗体系也是不同的，这也是一个问题。与欧洲、美国先进的治疗方法相比，日本、韩国和中国有很多古老传统的治疗方法。