Combining taxanes with radiation for solid tumors (2000)

Solid tumors present a significant treatment challenge because of poor overall cure rate. However, increasing use of chemotherapy and radiation may lead to improved local control as well as overall survival of patients with many locally advanced solid tumors treated traditionally with radiation alone, surgery alone, or chemotherapy alone. Radiation therapy alone may fail, because of the inability to deliver therapeutic doses without unacceptable toxicities and because of the presence of a subpopulation of tumor cells that are relatively insensitive to radiation therapy [1]. Surgery alone may fail because of the presence of disease outside the surgical bed. Chemotherapy alone has limited activity against many common solid tumors [2]. The taxanes are a new class of plant-derived antineoplastic compounds that share a unique mechanism of cytotoxic action and significant demonstrable efficacy in a wide variety of malignancies [3-6]. Paclitaxel and docetaxel are the first members of this class to be used in clinical practice. Taxanes are mitotic inhibitors that stabilize microtubules by promoting their assembly and preventing depolymerization [7, 8]. After exposure to the taxanes, cells are arrested in the G2/M phase of the cell cycle, which is known to be the most radiosensitive phase of the cell cycle [9, 10]. In addition to cell-cycle synchronization in G2M, other effects have been observed, increased apoptosis with paclitaxel in cell culture and in vivo [11]. Recently, the effects of paclitaxel were evaluated in 16 different murine tumors. A single 40 mg/kg dose of paclitaxel induced mitotic arrest to some degree in all tumor types, and apoptosis was observed in 50% of the tumors. The kinetics of mitotic arrest and apoptosis were studied in these tumors to determine the possible mechanism of taxane effects. Apoptosis, rather than mitotic arrest, appeared to predict efficacy (as determined by the delay in tumor growth) [11]. Tumor reoxygenation and repopulation as a result of taxane exposure also may be important in radiation enhancement [12]. The radiation sensitizing effects of taxanes are seen at very low drug levels, well below the levels required for cytotoxic effects. Numerous studies have demonstrated the radiosensitizing properties of paclitaxel in various cell lines [13-18]. Docetaxel also has been shown to enhance response to radiation with induced mitotic arrest and apoptosis in murine tumor cells [12, 19]. The effects of taxane exposure have been studied with numerous human cell lines derived from tumors of the lung [15, 20-23], head and neck [24-27], brain [28, 17, 18], breast [15, 20, 29, 22], colon [29], pancreas [15], ovary [15, 20, 30], cervix [14, 25, 16, 31], vulva [32], and prostate [33, 29], and from melanoma [21] and leukemia [13] cells. A supra-additive effect was observed most frequently, but additive or subadditive effects also were demonstrated under some experimental conditions. The extent of enhancement of the taxane-radiation interaction is dependent upon the specific cell line, growth status, and intensity and duration of drug exposure. Most in vivo studies analyzing taxane-induced radiopotentiation focused on paclitaxel and characterized both paclitaxel-sensitive and paclitaxel-resistant tumor types [11]. Radiation-induced inhibition of tumor growth is possible even in tumors resistant to single-agent paclitaxel, and the effect of the taxanes on the radioresponse of normal tissues are clearly less significant. The results of preclinical studies also suggest the timing of exposure to paclitaxel relative to radiation may be critical, and the optimal timing may vary depending on the sensitivity of tumor type to the taxane. Preclinical evidence also indicates possible applications of docetaxel in combined modality therapy. Collectively, these observations form a compelling basis for the continued design of clinical trials including the taxanes in chemoradiation treatment. Combined-modality therapy including paclitaxel or docetaxel results in substantial responses in several tumor types. Extensive experience has been gained with nonsmall-cell lung cancer, head and neck tumors, and esophageal tumors. Additional information will be required to determine the optimal dose and schedule of taxanes for different tumor types, the exact mechanism of action of taxane-induced radiosensitization, and the most effective use of radiation therapy in combined modality therapy. This review highlights recent clinical trials of the taxanes in combination with radiation therapy for solid tumors. Concurrent chemotherapy and radiation therapy trials have demonstrated a benefit to the combined synergism shown by a variety of radiosensitive agents such as hydroxyurea [34], misonidazole [35, 36], mitomycin C and cisplatin [37-39], and cisplatin plus FU [40]. Radiation therapy combined with cisplatin therapy [41-43] has been associated with high levels of partial and complete tumor response in patients with locally advanced head and neck cancer. Numerous phase I and II trials have evaluated various paclitaxel doses and administration schedules (as a single agent and in combination with other chemotherapeutic agents) plus radiation therapy in patients with locally advanced head and neck cancer (See Table 1) [44-47]. Main toxicities included mucositis, skin toxicity, and myelosuppression, although toxicities generally were manageable. Response rates were encouraging, with complete response rates ranging from 50% to 75% and overall response rates of 90% to 100%. Two phase II trials evaluated paclitaxel/platinum chemoradiation regimens in patients with locoregionally advanced head and neck cancers [48, 49]. One phase II trial [48] assessed weekly paclitaxel/carboplatin with concurrent radiation therapy, and one phase II trial [49] assessed induction chemotherapy with paclitaxel/carboplatin and concurrent radiation therapy and follow-up chemotherapy with 5-FU, interferon alpha, and cisplatin. Results of these trials were encouraging, with complete response rates of 57% to 78%. Principal toxicities included mucositis, skin toxicity, and myelosuppression. Amrein et al. [44] I Concurrent CT/RT Paclitaxel (60 mg/m2) 70.4 Gy 13 9 (69) 13 (100) Kroog et al. [45] I Concurrent CT/RT Paclitaxel (105 mg/m2) 70.2–72.0 Gy 16 12 (75) NR Machtay et al. [46] I Concurrent CT/RT Paclitaxel (40–120 mg/m2) 70–72 Gy 10 6 (60) 9 (90) Steinberg et al. [47] I Concurrent CT/RT Paclitaxel (70 or 105 mg/m2) 66–72 Gy 10 5 (50) 10 (100) Chougule et al. [48, 130] II Concurrent CT/RT Paclitaxel (60 mg/m2); carboplatin (AUC 1) 72 Gy 32 17 (57) 27 (90) Gonzalez et al. [49] II Induction CT/RT + Follow-up CT Induction: Paclitaxel (200 mg/m2); carboplatin (AUC 5) follow-up: 5-FU (1000 mg/m2/dx5); interferon alpha (5×106 u/m2); cisplatin (100 mg/m2) 60 Gy 29 28 (78) NR More recently, paclitaxel was added to the FHX (5-FU/hydroxyurea plus radiation therapy) regimen to enhance locoregional control and treat systemic micrometastatic disease. In a phase I trial, 55 patients with poor-prognosis head and neck cancer received 14-day cycles of 5-FU (600–800 mg/m2/d for 5 days), hydroxyurea (500 or 1,000 mg twice daily for 11 days), and escalating paclitaxel doses (5 to 25 mg/m2 per day for 5 days) plus concurrent radiation therapy (2 Gy on days 2 through 6 or 1.5 Gy twice daily) and G-CSF support [50]. The addition of paclitaxel to the FHX regimen is feasible, and patients generally experienced less toxicity with this regimen than with the cisplatin-FHX regimen. Consequently, a phase II study of the paclitaxel FHX regimen was initiated in previously untreated patients with locoregionally advanced head and neck cancer [51]. At a median follow-up of 10 months, 29 of 57 patients had achieved a complete response, and 14 of 57 patients had achieved a partial response, for an overall response rate of 75%. Therefore, this intensive concurrent chemoradiotherapy regimen resulted in encouraging locoregional control in patients with advanced disease. The Radiation Therapy and Oncology Group (RTOG) is conducting a 3-arm randomized phase II trial in locally-advanced patients to evaluate the toxicity and efficacy of three novel concomitant regimens: daily radiation (70 Gy/7wk) with weekly cisplatin and paclitaxel; 70 Gy/7 wk with daily cisplatin and 5-fluorouracil given over the last 10 days of radiation; and 70 Gy/13 wk given concurrently with daily 5-fluorouracil and hydroxyurea. A phase I/II trial explored the use of induction chemotherapy followed by radiation therapy in 23 previously untreated patients with advanced squamous cell carcinoma of the head and neck [52]. Induction chemotherapy consisted of docetaxel (25, 45, or 60 mg/m2 with and without growth factor support) plus cisplatin (25 mg/m2), 5-FU (700 mg/m2), and leucovorin (500 mg/m2) (PFL) every 28 days for up to three cycles; 72 to 74 Gy of radiation therapy was administered to the primary site after induction chemotherapy. The maximum tolerated dose (MTD) of docetaxel was 60 mg/m2 when combined with the PFL regimen. The dose-limiting toxicity (DLT) was neutropenia. Other major toxicities included nausea, mucositis, diarrhea, and peripheral neuropathy. In 22 evaluable patients, clinical complete responses at the primary site were observed in 19 patients (86%), and clinical partial responses were observed in 3 patients (14%), for an overall response rate of 100%. The encouraging results of this study merit further evaluation of this combination. An ongoing phase I study is evaluating induction chemotherapy followed by weekly 1-hour docetaxel infusions and concurrent radiotherapy for 6 weeks in previously untreated patients with advanced squamous cell carcinoma of the head and neck [53]. In general, concurrent taxane and radiation therapy is associated with high CR at the primary site and a high level of organ preservation or functional restoration (if ablation was done). Continued investigation of these and other taxane-based regimens is warranted. Combined thoracic radiation and chemotherapy, either sequentially or concurrently, has become the treatment of choice for unresectable stage III nonsmall-cell lung cancer [54]. Cisplatin has proved to be an important component of the chemotherapeutic agents used in randomized trials conducted to date that demonstrated an advantage of chemoradiotherapy [55-57]. Both taxanes have substantial activity as observed in phase II studies of previously untreated patients with metastatic nonsmall-cell lung cancer [5, 6, 58-65]. Their radiosensitizing properties stimulate continued interest in combined chemoradiation therapy using these agents [13]. Paclitaxel, as a single agent and also combined with other chemotherapeutic agents, has been investigated in several phase I and II studies in combination with radiation therapy in patients with unresectable, stage III nonsmall-cell lung cancer (see Table 2) [66, 67, 68, 69, 70]. A series of studies at Brown University and at Vanderbilt University [66, 67, 71, 72] assessed paclitaxel and concurrent radiation therapy. The MTD and DLTs of paclitaxel with concurrent thoracic radiation were determined in a phase I study in which paclitaxel was administered weekly as a 3-hour infusion, start- ing at 10 mg/m2 per week [62]. Over a period of 6 weeks, 27 patients were treated with paclitaxel at seven different dose levels, ranging from 10 to 70 mg/m2 per week, with concomitant chest irradiation (60 Gy total). The MTD of paclitaxel was 60 mg/m2 per week, and reversible esophagitis was the principal DLT. Paclitaxel + RT Choy et al. [66] I Concurrent CT/RT 25 NR NR NR NR Lau et al. [68] I Concurrent CT/RT 25 3 (12) 20 (80) NR NR Choy et al. [67] II Concurrent CT/RT 29 3 (10) 25 (86) 20 >61 Paclitaxel + platinum agents + RT Choy et al. [131] II Concurrent CT/RT + 37 6 (16) 28 (76) 20.5 56 follow-up CT Choy et al. [71] II Concurrent CT/RT + 42 3 (7) 33 (79) NR 63 follow-up CT Belani et al. [73, 77, 132] II Concurrent CT/RT 38 NR NR 19 61 Lau [133] II Concurrent CT/RT + 17 2 (12) 10 (59) NR NR consolidation CT Socinski et al. [74, 75] I Induction CT + 25 0 17 (68) NR 74 concurrent CT/RT Langer et al. [62] Induction CT + 29 2 (7) 17 (59) 14 62 concurrent CT/RT Greco et al. [76] II Induction CT + 29 12 (41) 24 (82) NR 60 concurrent CT/RT In another phase I trial, Lau et al. [68] evaluated paclitaxel administered twice weekly plus concurrent radiation therapy in 26 patients with locally advanced, unresectable nonsmall-cell lung cancer. In 25 evaluable patients, three (12%) achieved a complete response, and 17 (68%) achieved a partial response, for an overall response rate of 80%. The most common toxicity was esophagitis, which occurred in approximately 50% of patients who received paclitaxel doses >30 mg/m2 twice weekly. Choy et al. [67, 71, 72] conducted three prospective phase II studies of concurrent weekly paclitaxel and radiation therapy for patients with unresectable stage IIIA/IIIB nonsmall-cell lung cancer. One hundred fifteen patients, 73 males and 42 females, from 17 institutions were entered from April 1994 to May 1997. The median age was 61 years ranging from 36 to 85 years. There were 53 squamous cell carcinomas, 29 adenocarcinomas, 27 large cell carcinomas, and 6 poorly differentiated. The performance status was 0 in 46 of the patients and 1 in 69 of the patients. Thirty-seven patients had stage IIIA and 79 had IIIB disease. Trial 1 [67] used weekly paclitaxel (60 mg/m2 × 6) with radiation (60 Gy). The second trial [72] used weekly paclitaxel (50 mg/m2) plus weekly carboplatin (AUC 2 × 7) with radiation (66 Gy) followed by 2 cycles of paclitaxel (200 mg/m2) and carboplatin (AUC 6). The third trial [71] gave weekly paclitaxel/carboplatin (50 mg/m2/AUC 2 × 6) with hyperfractionated radiation therapy (1.2 Gy/BID/69.6 Gy) followed by 2 cycles of paclitaxel (200 mg/m2) and carboplatin (AUC 6). Of the 115 patients, 33 received paclitaxel plus radiation, 39 received paclitaxel/carboplatin plus radiation, and 43 received paclitaxel/carboplatin plus hyperfractionated radiation. The response rates of the three trials were 76%, 75.7%, and 78.65% respectively. The overall response rate among the three trials was 76.7%. The incidence of esophagitis (≥ grade 3) was 17%, 25%, and 26% for the individual trials, producing an overall incidence of 23%. Histological makeup varied between the trials with the proportion of squamous carcinoma vs. nonsquamous carcinoma in the first trial 57%/43%, in the second trial 52%/48%, and in the third trial 33%/67%. Overall, the distribution was 46%/54%. The 1-year overall survival for the three trials was 66%, 54%, and 61% respectively giving an average overall 1-year survival of 62%. The 2-year overall survival rate in the three studies was 36%, 46%, and 35% respectively, producing an average overall 2-year survival of 41%. The 3-year overall survival has been reached for the first two studies at 15% and 32%, giving an average of 26%. The third study has yet to reach 3 years follow-up time. Median survival in months for the three trials was 20, 20.5, and 14.3, with an average of 16 months. The median survival differences between squamous and nonsquamous indicated that squamous carcinomas had better median survival than nonsquamous, with the average median survival squamous/nonsquamous in the three trials as follows, 20/19.7, 26.8/18.2, and 20/13.2, with an average among the three of 22.5/16.2. However, this difference was not found to be statistically significant (P = 0.18). The frequency of SQ decreased during this interval. Age, stage, PS, toxicity, and pattern of failure were between statistically significant survival differences between the studies (P = and response with survival (P survival further evaluation of this regimen in phase III Other trials of chemoradiotherapy with paclitaxel/platinum compounds various paclitaxel doses and administration schedules Induction chemotherapy was used in some in which concurrent chemoradiation therapy with paclitaxel and platinum was initiated after Results of these trials also are encouraging, with overall response rates of to and 1-year survival rates of to Results of recent trials of paclitaxel/carboplatin and radiation therapy have demonstrated toxicity and the of chemoradiation therapy for locally advanced nonsmall-cell lung cancer and trials are conducted by the large in the phase II and III trials are evaluating the of of paclitaxel as well as induction chemotherapy with paclitaxel plus concurrent chemoradiotherapy In the trial induction chemotherapy with concomitant chemoradiotherapy is with stage IIIB nonsmall-cell lung cancer are cycles of cisplatin with two cycles administered concurrently with mg/m2 paclitaxel mg/m2 or 25 mg/m2 and a of 60 Gy of radiation. In an of the results of this trial, the in all three study generally were In the trial, patients with stage IIIB nonsmall-cell lung cancer two cycles of induction chemotherapy with paclitaxel mg/m2 and carboplatin (AUC followed by paclitaxel mg/m2 per week and carboplatin (AUC 2) weekly with concurrent radiation therapy. The results of this trial will determine the for a randomized phase III trial in which patients will either concurrent chemoradiotherapy with paclitaxel/carboplatin or two cycles of induction chemotherapy with paclitaxel/carboplatin followed by concurrent chemoradiotherapy with paclitaxel/carboplatin The Oncology Group is to a trial of induction paclitaxel/carboplatin followed by weekly paclitaxel/carboplatin plus concurrent radiation therapy and consolidation paclitaxel/carboplatin in patients with unresectable stage III nonsmall-cell lung cancer The is conducting a phase II trial of induction paclitaxel/carboplatin followed by paclitaxel/carboplatin plus concurrent radiation therapy, with or without for Results of these ongoing trials further the of chemoradiation therapy in patients with unresectable stage III nonsmall-cell lung cancer. Preclinical that docetaxel has radiosensitizing properties [9, and clinical trials of docetaxel plus radiation therapy have been initiated in patients with nonsmall-cell lung cancer and esophageal cancer In a recent phase I study to determine the maximum tolerated dose and optimal schedule of docetaxel with concurrent 29 patients with nonsmall-cell lung cancer and with esophageal received docetaxel 40 mg/m2 on day 1 of docetaxel 20 mg/m2 on days 1 and of or docetaxel 20 mg/m2 week of cycles; doses were to 60 mg/m2 per cycle and mg/m2 per cycle, with a weekly administration schedule used in some patients. Concurrent radiotherapy was administered at daily doses of to Gy for a dose of to 70 the radiation the overall response rate was among 20 evaluable patients with nonsmall-cell lung cancer and among 9 evaluable patients with esophageal cancer. and were the dose-limiting The maximum tolerated doses of with concurrent radiation therapy were 40 mg/m2 per cycle when given as one or two doses per cycle and 60 mg/m2 when given as three doses per cycle 20 mg/m2 concurrent docetaxel and radiation therapy appeared to be feasible, the was and further studies are warranted. phase I trial evaluated docetaxel 20 to 40 mg/m2 per week plus concurrent radiation therapy Gy) primary with 20 Gy in 11 patients with unresectable stage III nonsmall-cell lung cancer. Response and survival are not yet grade toxicities esophagitis, and skin were observed in all dose investigation is to determine the of docetaxel in therapy for unresectable stage III nonsmall-cell lung cancer. have evaluated chemotherapy and radiation therapy in patients with lung cancer et al. a phase I/II trial of paclitaxel, and with concurrent radiation for lung carcinoma to determine the of paclitaxel to and thoracic patients were in this the phase I of this the dose of paclitaxel was in of three or patients. were every cycles 1 and paclitaxel was administered to the at doses of or mg/m2 over 3 on day cycles 3 and the paclitaxel dose was at mg/m2 in all patients. day cisplatin 60 mg/m2 was administered for all days and 60 mg/m2/d 1 and 2) or mg/m2/d 3 and was radiation was given at 9 in for 5 weeks on day 1 of cycle The MTD of paclitaxel was with the dose-limiting toxicity grade neutropenia. 1 and 2 were associated with grade in 32%, with in of and grade esophagitis in 3 and were by grade in with in of and grade esophagitis in The overall response rate was partial After a median follow-up period of 23 months 9 to 40 the median survival was months to months In a phase II trial by et al. paclitaxel/carboplatin plus at two dose levels was evaluated with concurrent radiation therapy in 56 patients with lung cancer the 6 of evaluable patients achieved a complete response and patients achieved a partial response, for an overall response rate of the 29 of evaluable patients achieved a complete response and 11 patients achieved a partial response, for an overall response rate of Median survival was 17 months for the regimen and was months for the regimen. Both regimens were generally well with a incidence of observed with the regimen. Other grade toxicities included esophagitis, and An ongoing phase II trial is evaluating the addition of paclitaxel to plus radiation therapy in patients with lung cancer In 20 evaluable patients 16 achieved a complete response and 3 achieved a partial response for an overall response rate of The regimen was generally well the most common grade toxicities included and 3 esophagitis was observed in 2 patients. Other trials evaluating chemoradiation therapy in lung cancer are ongoing by and the Oncology Group The results of these trials to a better of the of dose and schedule of paclitaxel in chemoradiation therapy for lung cancer. on docetaxel in therapy for lung cancer have been one new chemotherapeutic agent and one new treatment are evaluated in randomized clinical trials for lung cancer The status of in this the for evaluation of new The for the use of paclitaxel to treat brain tumors activity in a wide of solid tumors, in and in vivo evidence of against primary brain tumors and a of effective irradiation a of therapy for primary and metastatic brain tumors, the of trials paclitaxel as a was The in radiosensitizing properties of paclitaxel and activity against cell lines the design of several recent trials using therapy for primary brain tumors. study of concurrent paclitaxel with clinical benefit of concurrent and phase I and phase II trials significant to concurrent in primary brain tumors In addition to these trials, a phase II study was conducted by to evaluate the use of paclitaxel with irradiation for Concurrent paclitaxel and radiation therapy for the treatment of metastatic brain tumors was also studied in a phase III trial This trial was conducted for patients with than 3 brain The of this trial was that paclitaxel with radiation therapy better brain tumor control of and better systemic tumor control of activity against solid and better overall survival with radiation therapy alone in this poor shown in Table patients radiation therapy with concurrent paclitaxel had better median survival with patients treated with radiation in most of chemotherapy the differences not reach study of the of paclitaxel in patients with brain tumors is and the optimal dose and schedule of administration are in the treatment of this tumor as for Docetaxel has not been used in the treatment of brain tumors, either in chemotherapy or chemoradiotherapy In a phase II trial of docetaxel mg/m2 therapy was or mg/m2 chemotherapy was in patients with (5 with and the with other complete or partial responses were A of was observed in a single study of a with these are the clinical benefit of concurrent taxane and radiation therapy to be at Paclitaxel has substantial single-agent activity in advanced or metastatic esophageal cancer, with Paclitaxel, is under investigation in chemoradiation regimens in combination with cisplatin or cisplatin plus 5-FU Paclitaxel was evaluated at various doses and administration schedules (see Table results of these trials are encouraging, with overall response rates in phase II trials ranging from to The average complete response rates from these trials was Principal grade toxicities included esophagitis and myelosuppression. Additional phase I and II trials are in to the use of paclitaxel in combination with cisplatin or carboplatin as therapy in patients with esophageal cancer and in patients with unresectable locally advanced or metastatic esophageal cancer Results of these trials further the of chemoradiation therapy in esophageal cancer. et al. I/II 5-FU 9 NR NR NR NR et al. I/II 5-FU 40 12 NR NR et al. II 5-FU 32 16 (50) 26 NR 62 et al. II cisplatin 22 NR NR et al. II paclitaxel leucovorin 19 3 (16) NR NR on docetaxel in therapy for esophageal cancer are Two recent phase I trials evaluated docetaxel 40 to mg/m2 per cycle with concurrent radiation therapy at 2 in patients with advanced unresectable including esophageal cancer The in one trial were 40 mg/m2 per cycle when administered every 3 weeks or for 2 weeks of every 3 weeks and 60 mg/m2 per cycle when administered weekly for 3 weeks 20 the MTD of docetaxel in the other phase I trial was 20 mg/m2 per week in combination with radiation therapy and were the DLTs responses were observed in both encouraging further investigation of docetaxel in therapy for esophageal cancer. A weekly paclitaxel and concurrent radiation therapy trial was for the treatment of cancer Paclitaxel to 60 mg/m2 over 3 was administered weekly for 6 weeks with concurrent radiation therapy (50 Gy in 28 of Gy in patients with locally advanced = or = cancer. activity was observed in this study against both and the 13 patients with cancer evaluable for response, were complete responses and partial for an overall response rate of the 10 evaluable patients with cancer, were complete responses and seven partial for an overall response rate of The dose-limiting toxicities in this study were the nausea, and which occurred at a paclitaxel dose of 60 Two phase II studies were initiated to evaluate paclitaxel with concurrent radiation therapy a dose of Gy) in patients with locally advanced and cancers After the of 25 patients in the cancer trial, 6 of evaluable patients achieved a partial response, for a response rate of toxicities included and the first 16 patients with cancer, 1 complete response and partial responses were observed, for an overall response rate of In this trial, grade toxicities observed included nausea, esophagitis, and In 24 patients with of the were complete responses and 14 partial for an overall response rate of 75%. toxicities included nausea, and trials demonstrated that chemoradiation including paclitaxel is well tolerated and has substantial activity against locally advanced trials are evaluating paclitaxel with concurrent radiotherapy for and cancers Results of these trials further the of chemoradiation therapy for these tumor types. The of docetaxel in combined modality therapy for cancers has not been results of phase II clinical trials have the single-agent activity of docetaxel against cancers investigation is Paclitaxel is as a single agent against breast cancer and radiosensitizing properties were demonstrated both in and in vivo results of a trial paclitaxel plus radiation therapy in patients with locally advanced breast cancer were received paclitaxel 60 plus radiation therapy (50 Gy in 2 Gy over 5 of toxicity experienced by the first two patients, the chemotherapy regimen was to paclitaxel mg/m2 twice weekly. were and received follow-up chemotherapy. Of the 13 patients patients are evaluable for response and The schedule was and patients achieved a response complete and partial of with response will be in a of patients in this of sensitivity to paclitaxel in several cell types and of tumor may lead to better for taxane-based treatment. docetaxel is against breast cancer results of clinical trials evaluating docetaxel in therapy for breast cancer have been to In recent the activity of taxanes (as single agents and in combination with other chemotherapeutic agents) plus radiation therapy has been evaluated in various tumor types. locally advanced nonsmall-cell lung cancer, results from phase I and II trials that therapy is generally well tolerated and control of local and metastatic disease. paclitaxel administration including weekly and are evaluated in combination with and hyperfractionated radiation therapy. platinum compounds to regimens are also encouraging trials are evaluating docetaxel plus radiation therapy in patients with locally advanced unresectable lung cancer. chemotherapy plus radiation therapy is explored for lung cancer, poor-prognosis squamous cell carcinoma of the head and esophageal cancer, brain tumors, and and locally advanced breast cancer. trials also are to evaluate concurrent paclitaxel and radiotherapy for malignancies in tumor cells are the of a of with may in unique to radiation and chemotherapy, cytotoxic agents with novel of An evaluation of the response of tumors with to paclitaxel and radiation therapy also is of A better of the by lead to effective treatment and of the doses and administration schedules and lead to better treatment and for many of these common solid tumors.