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Results for “Pathologic Complete Response”

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PubMed1987

High-dose pulse chlorambucil in advanced, low-grade non-Hodgkin's lymphoma.

High-dose pulse chlorambucil was given orally at a dose of 16 mg/m2 daily for 5 consecutive days each month, as reported by Cadman et al. It was used to treat 33 patients with advanced, low-grade non-Hodgkin's lymphoma. With median follow-up of 4.2+ years, 70% of the patients achieved objective response. Eleven of 24 patients with follicular small cleaved cell lymphoma (FSCL) had pathological complete response; nine of 24 with FSCL and three of seven with small lymphocytic lymphoma had partial response. Median disease-free survival was 28 months. Actuarial survival for all patients was 60% at 5 years from initiation of therapy. Treatment toxicity was minimal. Pulse chlorambucil is an effective and minimally toxic palliative therapy for advanced FSCL.

Administration, Oral↗

PubMed1986

Intra-arterial chemotherapy as an adjuvant to surgery in transitional cell carcinoma of the bladder.

Regional chemotherapy with intra-arterial cis-platinum and doxorubicin as an adjuvant to total cystectomy and urinary diversion has been evaluated in a phase I to II study. In the first 17 patients chemotherapy consisted of 40 to 75 mg. per m. cis-platinum intra-arterially during 30 minutes, 30 to 40 mg. per m. doxorubicin intra-arterially during 60 minutes (11 patients) or 12 hours (6 patients) and 400 to 500 mg. per m. cyclophosphamide intravenously. The remaining 8 patients received 70 to 100 mg. per m. cis-platinum intra-arterially during 30 minutes. Intra-arterial chemotherapy was administered through a percutaneous catheter placed in the hypogastric artery before each course. Courses were repeated at 4-week intervals. A total of 25 patients received 58 courses (median 2 per patient). Clinical stages of disease in the patients entering the protocol were T3aNxMo (8), T3bNx-2Mo (12) and T4a-bNxMx-1 (5). Clinical response was assessed in 24 of 25 patients: 6 achieved a complete clinical response, 12 had a partial response and 7 had no response. Of 25 patients 16 underwent total cystectomy and urinary diversion with pathological staging as follows: ToNoMo in 3, T1NoMo in 1, T3aNoMo in 5, T3bNo-2Mo in 6 and T4NoMo in 1. Intra-arterial chemotherapy can produce a complete pathological response in patients with locally advanced bladder cancer and is tolerated well by most patients.

Aged↗

PubMed1996

[Preliminary results of a phase II randomized controlled trial comparing M-VAC and M-CAVI in patients with bladder cancer (T2-4 N0-1 M0)].

OBJECTIVES: The combination of carboplatin, methotrexate and vinblastine (M-CAVI) is an active and well-tolerated regimen for patients with bladder cancer who are ineligible for cisplatin-based regimens. We have prospectively randomized patients with locally advanced (T2-4 N0 M0) or locoregional (Tx N1 M0) bladder cancer suitable for subsequent surgical treatment to M-VAC or M-CAVI chemotherapy. METHODS: M-CAVI consisted of carboplatin (300 mg/m2 on day 1 and later adjusted to 4.5 mg/dl/min according to Calvert's formula), methotrexate (30 mg/m2 on days 1, 15 and 22) and vinblastine (3 mg/m2 on days 1, 15 and 22). After 3-4 cycles, the patients were assessed for surgical resection. RESULTS: To date, 60 patients have been included. There were 58 completely evaluable patients, 27 were randomized to M-VAC and 31 to M-CAVI. The overall response rates were similar for M-VAC (48%; confidence interval 95%, 26%-67%) and M-CAVI (45%; confidence interval 95%, 28%-62%). The pathological complete responses were similar for the M-VAC and M-CAVI regimens for both the group with locally advanced (27% vs 39%, p = NS) and locoregional (14% vs 14%, p = NS) bladder cancer. The median actuarial survival for the M-VAC treated group was 23 months and 18 months for the M-CAVI. M-VAC therapy was statistically significantly associated with more events of granulocytopenic fever, grade 2-3 nausea and vomiting, grade 2 alopecia and grade 3-4 mucositis. CONCLUSIONS: The results achieved in the 60 patients included in the study indicate that M-CAVI is better tolerated than M-VAC, although both treatment regimens have similar overall response rates, pathological response rates and survival in patients with locally advanced and locoregional bladder cancer.

Adolescent↗

PubMed1990

High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer.

PURPOSE: To compare cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide as primary chemotherapy for stage III (suboptimal) and stage IV ovarian cancer. PATIENTS AND METHODS: Three hundred forty-two patients were randomly assigned to treatment with six courses of intravenous (i.v.) cisplatin 100 mg/m2 plus i.v. cyclophosphamide 600 mg/m2, or i.v. carboplatin 300 mg/m2 plus i.v. cyclophosphamide 600 mg/m2. RESULTS: The estimated median survivals were 17.4 and 20.0 months for the cisplatin and carboplatin study arms, respectively. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the P = .02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. Pathologic complete response rates were similar for both study arms. There was less thrombocytopenia on the cisplatin arm (P less than .001); however, there was less nausea and emesis (P less than or equal to .001 for courses 1 to 5), renal toxicity (P less than .001), anemia (P = .01), hearing loss (P less than .001), tinnitus (P = .01), neuromuscular toxicities (P = .001), and alopecia (P less than .001) on the carboplatin arm. CONCLUSION: Carboplatin-cyclophosphamide proved to have a significantly better therapeutic index than cisplatin-cyclophosphamide in patients with stage III (suboptimal) and stage IV ovarian cancer.

Adult↗

PubMed2001

Vinorelbine, epirubicin, and methotrexate (VEM) as primary treatment in locally advanced breast cancer.

PURPOSE: This phase II trial of VEM (vinorelbine + epirubicine + methotrexate) in the treatment of locally advanced breast cancer was conducted to obtain downstaging to allow surgery and breast conservation. PATIENTS AND METHODS: This multicenter study recruited 58 patients with locally advanced breast cancer (two patients ineligible); 56 were evaluable for response and tolerance. RESULTS: Downstaging was obtained in 77% of the patients with a pathological complete response (pCR) rate of 9%. At 33 months of follow-up, median survival has not been reached. Neutropenia grade 3-4 was reported in 31% of cycles with 3% of cycles with infection grade 3. Alopecia grade 3 was noticed for 71% of patients. CONCLUSION: VEM represents an effective regimen for patients with locally advanced breast cancer, allowing an important pCR. Moreover, this regimen appears to be particularly well tolerated.

Adolescent↗

PubMed2001

Positive emission tomography for evaluating a complete clinical response in patients with ovarian or peritoneal carcinoma: correlation with second-look laparotomy.

OBJECTIVE: Positive emission tomography (PET) provides a novel means of imaging malignancies. The following study was undertaken to evaluate the predictive value of PET in determining a pathologic complete response in patients with advanced ovarian or peritoneal carcinoma who had a complete clinical response following primary chemotherapy. METHODS: Twenty-two patients with advanced-stage ovarian (N = 17) or peritoneal (N = 5) carcinoma who had achieved complete clinical and radiologic remission and normal CA-125 level after six cycles of chemotherapy and who had consented to a second look laparotomy procedure were studied. All patients received platinum based therapy and all but one patient, treated elsewhere, received paclitaxel in combination with platinum. Following IV administration of 20 mCi [(18)F]fluorodeoxyglucose (FDG), the entire abdomen and pelvis were scanned. Various technical modifications including bladder activity dilution, intravenous hydration with diuretic therapy, and mechanical bowel preparations, were used to reduce background activity. Second-look laparotomy findings were classified as negative, macroscopically positive if a biopsy of a suspicious area was histologically positive, or microscopically positive if only a nonsuspicious area was histologically positive. The effect of patient preparation prior to PET imaging was evaluated. RESULTS: Persistent disease was found in 13 of the 22 patients (59%). Only one of nine sites with macroscopic and none of four with microscopic disease were accurately predicted. The sensitivity was only 10% and the specificity 42%. Intravenous hydration, diuretic therapy, and bowel preparation did not improve the results. CONCLUSIONS: These results suggest that despite technical modifications the sensitivity of PET before second-look laparotomy for small-volume persistent disease is low.

Adenocarcinoma, Mucinous↗

PubMedDate not supplied

p53 status is neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen.

BACKGROUND: The aim of this study was to assess the relationship between p53 status and the clinical outcome of patients with advanced ovarian cancer treated with a paclitaxel-based regimen. PATIENTS AND METHODS: The investigation was conducted on 38 patients with FIGO stage III-IV ovarian cancer from whom tumor tissue samples for p53 protein immunostaining were obtained during initial cytoreductive surgery. All these patients subsequently received six cycles of first-line combination chemotherapy with paclitaxel 175 mg/m2 (3-hour infusion) plus carboplatin AUC 6 with or without epidoxorubicin 75 mg/m2. RESULTS: Positive p53 immunostaining was detected in tissue samples collected from 24 (63.2%) ovarian cancers. A clinical complete response was obtained in 14 (58.3%) of the 24 patients with positive p53 immunostaining compared to 9 (64.3%) of the 14 patients with negative p53 immunostaining (p = 0.717). A pathological complete response was found in 6 (25.0%) of the former compared to 4 (28.6%) of the latter (p = 0.956). Similarly, survival did not correlate with p53 status (p = 0.1271). DISCUSSION: p53 status seems to be neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen. These results are consistent with experimental data showing that paclitaxel cytotoxicity in ovarian cancer is likely to be mediated by a p53-independent pathway.

Adult↗

PubMed1990

Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy.

Thymic carcinomas are rare malignant neoplasms of the thymic epithelium that are distinguished from the malignant thymomas by the presence of cytologic atypia. Thymic carcinomas may metastasize outside of the thorax and are associated with a very poor prognosis. Complete responses of thymic carcinoma to chemotherapy alone have not been reported. A 21-year-old man with metastatic undifferentiated carcinoma of probable thymic origin is presented who achieved a pathologic complete response with cisplatin, vinblastine, and bleomycin chemotherapy. Additional consolidative chemotherapy with cisplatin and etoposide was administered. The patient remains disease-free 5 years after diagnosis. Cisplatin, vinblastine, and bleomycin chemotherapy appears to have significant activity against thymic carcinoma.

Adult↗

PubMed1999

Monitoring response to treatment in liver tumours.

New imaging techniques offer better ways of measuring response to treatment and remain central to the formal assessment of response in clinical trials and routine clinical practice. Increasing tumour size is consistently associated with progressive disease. However, there is evidence that the designation 'partial response', as determined by conventional imaging techniques, may not always accurately reflect the degree of treatment-induced tumour necrosis. Thus, responses classified as partial on imaging grounds have, in some cases, been shown to be complete pathological responses after surgical resection, implying that residual tumour and necrotic/fibrotic tumour remnants cannot always be accurately distinguished by imaging. In this situation, serological tumour markers such as alphafetoprotein may be useful in measuring the true degree of response. While radiological imaging is likely to remain the main method of assessing response in phase II trials of drugs for the treatment of liver cancer, it may in some instances be useful to apply additional parameters such as alphafetoprotein level.

Biomarkers, Tumor↗

PubMed2001

Issues involved in research into the neoadjuvant treatment of breast cancer.

Randomized studies have failed to find convincing evidence that neo-adjuvant chemotherapy results in improved overall survival. This may be related to limited efficacy of the regimens used. A sequence of an anthracycline-based primary chemotherapy followed by docetaxel has shown promising results which are briefly discussed. The assessment of the efficacy of neoadjuvant therapy should be based on the evaluation of pathological response and a simple, reproducible method of grading differential response would be of great value. Positive identification of tumor stroma is essential in defining pathological complete response (pCR). This paper presents a grading scheme based purely on microscopic assessment which classifies patients into five groups with significantly different disease-free and overall survival. A system dividing patients into only two groups, i.e. those with pCR or those with any evidence of invasive tumor, may lose information of prognostic value. Assessing the response of metastatic disease in the lymph nodes, as well as response of the primary tumor, may further refine our ability to identify those patients likely to gain most from neoadjuvant chemotherapy.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Alpha-fetoprotein in the management of germ cell tumors of the ovary.

From 1982 to 1989 positive alpha-fetoprotein (AFP) levels were detected after surgery in 3 patients with pure immature teratoma, 7 patients with mixed germ cell tumors and 16 patients with pure endodermal sinus tumor (EST) of the ovary. In the three patients with pure immature teratoma, AFP serum levels became spontaneously undetectable in one month without chemotherapy. The marker was thereafter negative, despite the persistence of tumor in 2 patients, and a relapse in the third one. The serum levels of AFP did not correlate with the stage of EST and mixed germ cell tumors. The monitoring of AFP serum levels during treatment correlated with response to chemotherapy: of the 16 patients with pure EST, 14 achieved a serological complete response and did not undergo second look surgery; two patients had a serological partial response. One of them reached a serological complete response after further chemotherapy. The other patient with liver extragonadic tumor underwent liver lobectomy with negative histology. Among 7 patients with mixed germ cell tumor, 6 achieved a serological and pathologic complete response. The 7th patient had a serological complete response, but microscopic residual tumor at second look laparotomy. The decrement curve of AFP was not predictive for recurrence. However, AFP monitoring was useful for an early diagnosis of relapse in 4 patients. AFP is a reliable marker for the diagnosis, treatment evaluation and follow-up of patients with pure EST and a useful marker in the clinical management of mixed germ cell tumors of the ovary.

Adolescent↗

PubMed1993

[Promising results of bimonthly chemotherapy with high dose cyclophosphamide and epirubicin in induction treatment of inflammatory cancer of the breast].

Forty-eight patients with inflammatory breast cancer were treated by an induction regimen with cyclophosphamide (1200 mg/m2), and epirubicin (75 mg/m2). Four to six courses were given every two weeks, whatever the absolute leukocyte counts, before mastectomy, loco-regional radiation, and conventional, or reinforced, for selected patients, chemotherapy. Main toxicity was leukopenia, with grade IV in 25% of cases. However, febrile neutropenia was rare, and relative dose intensity was 102% after four courses, and 97% after six courses. Complete disappearance of inflammatory signs was observed in 90% of patients. Three patients had a pathological complete response, and ten patients had negative axillary lymph nodes. Furthermore, 13 patients had a major pathological response. With a median follow-up of 42 months, progression-free survival and overall survival are 48% and 66%, respectively.

Adolescent↗

PubMed1999

Pretreatment staging by endoscopic ultrasonography does not predict complete response to neoadjuvant chemoradiation in patients with esophageal carcinoma.

BACKGROUND: Endoscopic ultrasonography (EUS) provides highly accurate preoperative T and N classifications in patients with esophageal carcinoma. Although previous data have suggested that patients with tumors classified as T4 by EUS do not benefit from surgical resection, these data were acquired prior to the widespread use of preoperative chemoradiation. The current study investigated whether pretreatment EUS can predict a complete response to neoadjuvant therapy. METHODS: Patients with esophageal carcinoma (adenocarcinoma or squamous cell carcinoma) underwent EUS classification prior to therapy. Patients classified as T2, T3, or T4 and M0 were treated with 5-fluorouracil, cisplatin, and radiation under protocol. Patients with T1 lesions underwent resection without prior chemoradiation. Chemoradiation was followed in all cases by attempted surgical resection. The initial EUS classification was compared with the final pathologic results. RESULTS: Fifty-five patients (47 males and 8 females) with a mean age of 60.5 years (range, 31-78 years) were evaluated. There were 41 adenocarcinomas and 14 squamous cell carcinomas. Among the total population, a complete response was achieved in 3 of 5 patients (60%) with tumors classified as T2 by EUS, 14 of 42 patients (33%) with tumors classified as T3 by EUS, and 5 of 8 patients (63%) with tumors classified as T4 by EUS (P = 0.19). A complete response was achieved in 9 of 24 patients (38%) found to have N0 disease by EUS versus 13 of 30 patients (43%) determined to have N1 disease (P = 0.66). The results for patients with adenocarcinoma and squamous cell carcinoma were similar. CONCLUSIONS: The results of the current study demonstrate that pretreatment EUS does not predict reliably which patients with esophageal carcinoma will achieve a complete pathologic response to preoperative neoadjuvant chemoradiation.

Adenocarcinoma↗

PubMed1999

Biochemoprevention for dysplastic lesions of the upper aerodigestive tract.

OBJECTIVES: To evaluate the efficacy and secondarily the toxic effects of biochemopreventive therapy (high-dose isotretinoin [13-cis-retinoic acid], alpha-tocopherol, and interferon alfa) in the reversal of advanced premalignant lesions of the upper aerodigestive tract and to correlate the therapeutic events with modulation of biomarkers. DESIGN: Prospective, nonrandomized chemoprevention trial. SETTING: Tertiary cancer care referral center and ambulatory care. PARTICIPANTS: Thirty-six patients with advanced premalignant lesions of the upper aerodigestive tract, without cancer during the 2 years before the intervention, with evaluable lesions, and without retinoid therapy for 3 months before the trial. INTERVENTION: Administration of oral isotretinoin (100 mg/m2 per day), oral alpha-tocopherol (1200 IU/d), and subcutaneous interferon alfa (3 megaunits per square meter twice weekly) for 12 months, with serial biopsies and clinical examination at 0, 6, 12, and 18 months from study start. MAIN OUTCOME MEASURES: Clinical and histologic responses to the intervention. RESULTS: Of the 36 patients, evaluation was possible in 30 for response at 6 months and in 21 at 12 months. At 6 months, there were 10 pathologic complete responses and 7 partial responses; at 12 months, 7 complete and 3 partial responses. A striking difference in response was observed in favor of laryngeal lesions (9/19 [47%] complete response rate at 6 months and 7/14 [50%] at 12 months vs 1/11 [9%] and 0/7 [0%], respectively, for oral lesions). Toxic effects were acceptable and did not exceed grade 3. CONCLUSION: Biochemoprevention is a promising biologic approach for laryngeal dysplasia and needs to be investigated further.

Adult↗

PubMed2000

Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: a phase II dose escalation study.

PURPOSE: To study the impact of preoperative radiation dose escalation and postoperative adjuvant chemotherapy on the outcome of tethered and fixed rectal carcinoma. METHODS AND MATERIALS: We have treated 156 patients with 3 consecutive preoperative chemoradiation protocols with escalating treatment intensity. Schedule 1 consisted of 40 Gy radiation with concurrent 5-fluorouracil (5-FU) infusion and mitomycin C. Schedule 2 used a sandwich design with preoperative (40 Gy) and postoperative (18 Gy) radiation with concomitant 5-FU infusion, leucovorin, and mitomycin C. In schedule 3, the preoperative radiation dose was increased to 50 Gy and adjuvant 5-FU/leucovorin chemotherapy was added following surgery. There were 54, 27, and 75 patients treated in schedules 1, 2, and 3, respectively. RESULTS: The resectability was 91% for schedule 1 and 100% for both schedules 2 and 3. A dose-response relationship was observed between the radiation dose and the tumor downstaging and local control. The pathological complete response (T0N0M0) rates for schedules 1, 2, and 3 were 4%, 15%, and 25%, respectively. The respective rates of tumor downstaging were 41%, 33%, and 68%, respectively. The 5-year local relapse-free rates were 67% for schedule 1 (40 Gy), 96% for schedule 2 (58 Gy), and 92% for schedule 3 (50 Gy) (p = 0.0011). The addition of postoperative chemotherapy appeared to improve both the survival and the relapse-free survival. The 5-year survival was increased from 52% to 84% (p = 0.0004) and the 5-year progression-free survival was improved from 48% to 74% (p = 0.0008). CONCLUSION: Preoperative 5-FU infusion, leucovorin, mitomycin C, and 50-Gy pelvic radiation, followed by postoperative bolus 5-FU/leucovorin chemotherapy, appeared to be an effective treatment for tethered/fixed rectal cancers. However, its therapeutic efficacy could only be validated in randomized studies.

Adult↗

PubMed1996

M-CAVI, a neoadjuvant carboplatin-based regimen for the treatment of T2-4N0M0 carcinoma of the bladder.

Carboplatin, methotrexate, and vinblastine (M-CAVI) is an active and well-tolerated regimen for bladder cancer patients ineligible for cisplatin-based regimens. We treated 47 T2-4 N0 M0 bladder cancer patients with M-CAVI in a neoadjuvant phase II trial. These 47 patients are evaluable for clinical response and toxicity. Clinical overall response rate was 34%, for a 95% confidence interval (CI95%) of 21-49%. Pathological response was seen in 40% of the patients (CI95%, 26-56%) with a 26.5% rate of pathological complete response (CI95%, 15-42%). Factors associated with the achievement of a response to therapy were the initial TNM stage (pT3a or lower, greater than pT3a, p = 0.001) and a Karnofsky score greater or equal than 90%, which was marginally significant (p = 0.08). With a median follow-up of 14 months, the disease-specific actuarial survival at 2 years is 42%. No patient has relapsed beyond 21 months of follow-up in a disease-free status. Toxic effects have been moderate. In conclusion, M-CAVI is an active and well-tolerated regimen that should be compared in terms of response rate and survival with a cisplatin-based regimen for invasive bladder cancer.

Actuarial Analysis↗

PubMed2001

Addition of oxaliplatin to continuous fluorouracil, l-folinic acid, and concomitant radiotherapy in rectal cancer: the Lyon R 97-03 phase I trial.

PURPOSE: Oxaliplatin could increase the efficacy of fluorouracil (5-FU)/folinic acid chemoradiotherapy in rectal cancer. We tested three dose levels to identify a feasible oxaliplatin dose for combination therapy. PATIENTS AND METHODS: Between February 1998 and April 2000, we included 17 rectal adenocarcinoma patients in a single-center phase I study. Patients had T4 rectal carcinoma, T1-T3 disease with colostomy refusal, or potentially operable T2/T3 M1 requiring local treatment. Pelvic radiotherapy was 45 Gy over 5 weeks, 1.8 Gy/fraction, with concomitant chemotherapy weeks 1 and 5. Chemotherapy was oxaliplatin 80, 100, or 130 mg/m2 2-hour infusion on day 1 followed by L-folinic acid 100 mg/m2/d intravenous bolus, and 5-FU 350 mg/m2/d continuous infusion on days 1 to 5 (FolfoR1). Six patients refusing surgery received additional contact radiotherapy +/- brachytherapy. Dose escalation proceeded if less than two of six patients had dose-limiting toxicity (DLT) at a given dose-level. RESULTS: All except two patients completed treatment; patients at level 1 (prolonged grade 1 thrombocytopenia) and level 3 (prolonged cold-related dysesthesia) had no second chemotherapy course. Median follow-up is 14 months (range, 2 to 28 months). One elderly patient at dose level 1 had DLT asthenia, severe diarrhea and vomiting, and more than 10% weight loss. There were no other DLTs and no severe rectitis or gastrointestinal toxicity. There were objective responses at all doses and no progressions. Eight patients underwent radical surgery after chemoradiotherapy. Two had complete pathologic responses. CONCLUSION: FolfoR1 seems feasible and effective. Dose escalation did not increase toxicity. Although the MTD was not reached in this study, we recommend oxaliplatin 130 mg/m2 for phase II studies because it is the dose determined from studies in metastatic patients with no toxicity when given concurrently with radiation.

Adult↗