Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon alpha for metastatic melanoma: a multicentre phase II study.

High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis.     

Treatment of epidemic Kaposi's sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine

An epidemic of disseminated Kaposi's sarcoma in male homosexuals has recently been described. Forty-one evaluable patients with epidemic Kaposi's sarcoma were treated with etoposide. The majority of these patients had early stage disease, no prior opportunistic infections, and no prior therapy. Twelve patients (30%) achieved complete remission, 19 (46%) partial remission, and ten (24%) no response. With follow-up time to 31 months, the median response duration is nine months. The median survival of patients with complete and partial remissions has not been reached. A combination of doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), bleomycin, and vinblastine (ABV) was used in 31 evaluable patients with epidemic Kaposi's sarcoma. The majority of these patients had late stage disease, prior opportunistic infections, or had failed prior treatment. Seven patients (23%) achieved complete remission, 19 (61%) partial remission, and five (61%) no response. With follow-up time to 24 months, the median response duration is eight months. The projected median survival for all patients treated with ABV is nine months. Both regimens were well tolerated, with an overall response rate of 76% for etoposide and 84% for ABV. However, while successfully treating the Kaposi's sarcoma, the underlying immune deficiency in these patients has persisted. Future treatments of Kaposi's sarcoma will need to focus on reversing the underlying immune incompetence as well as controlling the malignant manifestations of Kaposi's sarcoma arising in relation to the acquired immune deficiency syndrome.     

Hexamethylmelamine,adriamycin, and cyclophosphamide (HAC) versus cis-dichlorodiamineplatinum,adriamycin, and cyclophosphamide (PAC) in advanced ovarian cancer: A randomized clinical trial

Summary After stratification according to diameter of the largest residual tumor, 120 previously untreated ovarian cancer patients were randomized to receive adriamycin and cyclophosphamide in combination with hexamethylmelamine (HAC) or cis-dichlorodiamineplatinum (PAC). The surgical response rates were 66% to HAC and 70% to PAC, with median times to progression of 14 and 22 months and median survival times of 23 and 24 months, respectively. In patients with residual tumor >2 cm the surgical response rates to HAC and PAC were 56% and 63%, with complete response rates of 13% and 21%, respectively. In two of five complete responders to HAC there has still been no progression at 38 and 48 months, with a median response duration of 25 months. Only one of the nine complete responders to PAC has relapsed, at 33 months, while in the eight others response is maintained at follow-up times of 35–64 months. Myelosuppression was generally mild and similar in the two arms. No significant nonhematological toxicity was reported. It is concluded that at a median follow-up time of 36 months HAC is as effective as PAC in terms of response, duration of remission, and survival in previously untreated advanced ovarian cancer.Part of the work reported in this paper has already been presented at the AACR Meetings in 1980 in San Diego (Proc Am Assoc Cancer Res 21: 148, Abs. 595) and in 1981 in Washington DC (Proc Am Assoc Cancer Res 22: 166 Abs. 660)     

A limited role for VEEP (vincristine, etoposide, epirubicin, prednisolone) chemotherapy in childhood Hodgkin's disease

The VEEP regimen (vincristine, etoposide, epirubicin, prednisolone), with or without involved field radiotherapy, has been shown to be an effective treatment in adult Hodgkin's disease. In an attempt to avoid the late sequelae of both alkylating agents and radiotherapy this regimen has been studied in a series of 54 children and young adults. Early analysis suggested that the relapse rate was higher with VEEP than with standard alkylating agent-based regimens. Sufficient follow-up has now been achieved to evaluate the likelihood of sustained remission following second-line treatment and therefore the overall long term survival with this treatment approach. The 5-year Overall Survival (OS) and 5-year Progression Free Survival (PFS) for patients with stage I-III disease was 93% and 82% respectively. However, the 5-year OS and PFS for stage IV patients was only 44% and 50%, respectively. Of 13 patients who were initial treatment failures on VEEP, 7 of whom had advanced disease, only 6 were salvaged with second-line therapy. 8 of 33 who attained a complete response (CR) relapsed and there were 2 relapses in those achieving a partial response (PR) (n = 8). All those relapsing from CR/PR were salvaged by second-line alkylating agent chemotherapy +/- radiotherapy, +/- high dose chemotherapy. In conclusion, patients with stage I-IIIA, non-bulky disease, the moderately high relapse rate did not adversely affect the overall high cure rate, although VEEP failures were subjected to a high total treatment burden. VEEP alone is inadequate in patients with stage IV disease, bulky mediastinal disease in/or those with B symptoms in whom there is a high primary failure rate and relatively poor results with second line therapy.     

Continuous cyclophosphamide, doxorubicin, vincristine, and prednisolone. A new, innovative protocol for diffuse aggressive lymphomas

One hundred eight patients with aggressive non-Hodgkin's lymphoma (high and intermediate grade) were treated with a new protocol: continuous cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). They were evaluated for long-term survival and pretreatment characteristics predictive of response and survival. Continuous CHOP protocol consists of initial 8 weeks of intensive chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone, followed by local/cranial radiotherapy and maintenance therapy. Complete remission (CR) was achieved in 84 of 108 (78%) patients; seven (6%) had a moderate response and 17 (16%) had a poor response. A statistically significant difference in CR rate was found only in patients with different stages. Seventeen of 84 (20%) complete responders have had a relapse of the disease. The median survival has not been reached. Results show an actuarial disease-free survival (DFS) of 77% for the 84 patients who had a complete response. The overall survival for all patients was 53% at 5 years of follow-up. The difference in DFS at the end of 5 years between different stages, main histologic subgroups, and age groups was not statistically significant. The toxicity observed was acceptable. Thus continuous CHOP appears to be an effective protocol for the treatment of intermediate-grade and high-grade lymphomas.     

Clinical effects of combination therapy with mitoxantrone,vincristine, and prednisolone in breast cancer

PURPOSE: We assessed the clinical efficacy and safety of mitoxantrone hydrochloride which has been used as an anticancer drug in our hospital to treat breast cancer patients since 1993. METHODS: A group of 23 patients with breast cancer were given one course of the following regimen every 3 weeks: mitoxantrone hydrochloride (8 mg/m(2) i.v. day 1), vincristine sulfate (1.2 mg/m(2) i.v. day 1), and prednisolone (30 mg orally days 1-7). RESULTS: The response rate was 52.2% including a complete response in four patients, and a partial response in eight patients. Adverse drug reactions included leukocytopenia (78.3%, 18/23 patients), alopecia (30.8%, 7/23), and peripheral neuropathy and generalized fatigue (26.1%, 6/23). In patients responding to the drug regimen, 50% survival was 29 months, and in those not responding it was 12 months. CONCLUSION: Combination treatment with mitoxantrone hydrochloride, vincristine sulfate and prednisolone is an effective treatment for breast cancer.     

Epirubicin, cisplatin, oral UFT, and leucovorin combination chemotherapy in advanced and metastatic esophageal cancer

Background: The purpose of treatment in patients with advanced and metastatic esophageal cancer is to improve symptoms and maintain quality of life. Recently, the regimen including epirubicin, cisplatin, and 5-FU (ECF) has been used with protracted venous infusion (PVI), and has been reported to be an effective treatment for advanced and metastatic csophagastric cancer. However, complications and the inconvenience associated with PVI cannot be justified for the treatment of advanced esophageal cancer. Therefore, we provided treatment with oral UFT and leucovorin instead of 5-FU PVI to improve convenience and catheter related complications. Patients and Methods: Thirty-seven patients with advanced esophageal cancer were admitted between March 2002 and April 2005. The treatment schedule was as follows: epirubicin 50 mg/m² iv on d 1, cisplatin 60 mg/m² iv on d 1, oral UFT 300 mg/m² and leucovorin 75 mg for 21 consecutive days of treatment followed by a 7-d treatment-free interval. Results: The response rate was 45.9% including one complete response (95% CI: 29.8%–62%). The median survival was 13 mo (95% CI: 10–16 mo). Four patients had adenocarcinoma. Interestingly, their response rate was 75% including one complete response. Myelosuppression was the most important toxicity. Other toxicities were tolerable. Conclusion: The combination of epirubicin, cisplatin, UFT, and leucovorin (EPUL) could be another alternative to ECF in patients with advanced esophageal cancer. And this treatment might be more effective in adenocarcinoma of esophageal cancer.     

Combination chemotherapy with adriamycin, cyclophosphamide, vincristine, prednisolone (VEPA) in non-Hodgkin's lymphoma, with special reference to correlation of surface phenotype with response and survival

Thirty-seven previously untreated patients with advanced non-Hodgkin's lymphoma were treated with VEPA therapy. The complete remission (CR) rate was higher in the patients with diffuse B-cell lymphoma (75%) than in those with follicular B-cell lymphoma (20%) and T-cell lymphoma (42%). Two characteristics, i.e., elevated LDH and bone marrow involvement, were negatively associated with response rate in patients with diffuse lymphoma (B-, T-). The median duration of CR has not yet been reached, and the 2-year relapse-free rate was 64% for cases of diffuse B-cell lymphoma, while for T-cell lymphoma patients, the median duration of CR was 7 months. For diffuse B-cell lymphoma patients, the median survival has not yet been reached, and the 2-year survival rate was 57%. On the other hand, median survival for T-cell lymphoma patients was 12 months. VEPA therapy was less effective for the treatment of T-cell lymphoma, and a more intensive regimen should therefore be designed to overcome the potential aggressiveness of T-cell lymphoma.     

Effectiveness of novel combination chemotherapy, consisting of 5-fluorouracil, vincristine, cyclophosphamide and etoposide, in the treatment of low-grade gliomas in children

Low-grade gliomas (LGG), which account for about 30% of brain tumors in children, are usually treated with surgical excision and/or radiotherapy. For patients who have significant residual tumor after resection or relapse after radiation, the proper chemotherapy regimen has not yet been identified. Thirteen children diagnosed with LGG outside the cerebellum between January 1999 and December 2004, all of whom had significant residual tumor after surgical resection, relapsed after radiation or showed visual deterioration, were treated for 18 months with a multi-drug regimen of vincristine, etoposide, cyclophosphamide and 5-fluorouracil. Of the 7 patients who completed chemotherapy, 1 showed complete response (CR), 5 showed partial response (PR), and 1 had stable disease (SD). In 5 patients, chemotherapy was prematurely discontinued; 4 of these patients showed tumor progression and 1 had SD. One patient is still undergoing treatment. The side effects of chemotherapy were manageable. The median time to tumor response was 34 months (range, 2–82 months). The progression free survival was 67.3%. Pediatric LGG patients with residual tumor after surgery or who undergo relapse(s) may be successfully treated using our combination chemotherapy regimen.     

ABLETOP, a well-tolerated, effective regimen for relapsing Hodgkin's disease. Swiss Group for Clinical Cancer Research (SAKK)

ABLETOP, a salvage regimen for relapsing Hodgkin's disease consisting of adriamycin, bleomycin and etoposide, has been evaluated in 18 patients, 16 of whom were evaluable for toxicity and 15 for response. Fourteen patients showed maximal grade II nausea and vomiting, whereas 13 patients had grade III/IV alopecia. The median leukocyte nadir was 3.1 x 10(3)/mm3. Twelve of 15 patients evaluable for response reached a complete or partial remission; 10 of 12 pretreated patients reached a remission, 5 a complete remission and 5 a partial remission, for an overall response rate of 83%. We conclude that ABLETOP is a well-tolerated effective regimen for relapsing Hodgkin's disease.     

A phase II evaluation of clofazimine plus doxorubicin in advanced, unresectable primary hepatocellular carcinoma.

The riminophenazine compound clofazimine has been shown to be a potent inhibitor of hepatocellular carcinoma (HCC) in vitro. Therapeutic benefit was claimed for patients with HCC treated with clofazimine in a recent clinical trial. The current trial was initiated to evaluate response and survival of patients with HCC receiving clofazimine plus doxorubicin. Twenty-eight patients were entered into the study, of whom 27 were evaluable for response and survival. No patients had a complete or partial response, and 9 had stable disease. The median survival time was 7 weeks. Toxicity was mild with yellow pigmentation of the skin resulting from the clofazimine, and leukopenia, nausea, vomiting and mucositis as expected from doxorubicin. Further studies using other riminophenazine compounds are warranted.     

Radiotherapy in the treatment of malignant mesothelioma of the pleura,with special reference to its use in palliation

Most patients presenting with malignant mesothelioma of the pleura (MMP) are only suitable for palliative treatment. Radiotherapy has not been shown to improve survival in patients with this disease, but is of use in the palliation of symptoms. In this retrospective review of 111 patients with MMP referred to the Peter MacCallum Cancer Institute, the palliative effect of radiotherapy was analysed. More than half of the patients whose response could be assessed had some symptomatic relief from the radiotherapy treatment. No dose–response relationship could be found.     

The efficacy of a combination of etoposide, ifosfamide, and cisplatin in the treatment of patients with soft tissue sarcoma

BACKGROUND: Successful chemotherapy for patients with soft tissue sarcoma (STS) has been limited by a lack of active drugs. The most effective single agents are doxorubicin, dacarbazine, and, more recently, ifosfamide. Previously the most widely used combination has been CYVADIC (cyclophosphamide, vincristine, doxorubicin, and dacarbazine). In one randomized trial, ifosfamide was superior to cyclophosphamide; two nonrandomized studies also reported favorable results. Etoposide monotherapy was successful in 8%; the effectiveness of cisplatin was 5-23%. In view of these findings, the authors treated STS patients with an etoposide, cisplatin, and ifosfamide (VIP) combination. METHODS: The eligibility criteria included histologically confirmed, inoperable, metastatic or locally recurrent STS; a World Health Organization (WHO) performance status of 0-2; a maximum age of 75 years; and progressive, measurable disease. A total of 104 patients were treated from January 1990 to June 1997. The median age of the patients was 42.4 years. The patients were treated with a combination of etoposide (100mg/m(2) for 5 days), ifosfamide (2000 mg/m(2) for 2 days), and cisplatin (20mg/m(2) for 5 days) once a month via a peripheral vein. The treatment response and the toxicity were assessed according to WHO criteria. RESULTS: Of 104 evaluable patients, 47 responded. The overall response rate was 46% (complete response: 10%; partial response: 36%). In 43 patients the disease remained stable (41%). Remission duration was 4.6 months. Toxicity was moderate. The main adverse events were alopecia (100%), nausea and vomiting (73%), and leukopenia (29%). CONCLUSIONS: This new combination is promising for the treatment of patients with advanced STS.     

Phase II study of docetaxel, doxorubicin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer.

PURPOSE: This pilot phase II study investigated the efficacy and toxicity of docetaxel with doxorubicin and cyclophosphamide (TAC) as first-line chemotherapy for anthracycline-naive patients with metastatic breast cancer. PATIENTS AND METHODS: Fifty-four patients received a total of 359 courses consisting of docetaxel 75 mg/m2 given intravenously (IV) over 1 hour, preceded by IV doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 for a maximum of eight 3-week cycles. RESULTS: After an independent panel review, the overall objective response rate was 77% (complete response, 6%). Overall objective response rates in patients with visceral, bone, and liver involvement were 82%, 82%, and 80%, respectively. Median duration of response was 52 weeks, and median time to progression was 42 weeks. With a median follow-up of 32 months, the median survival had not yet been reached, whereas the 2-year survival was 57%. The main toxicities were hematologic (neutropenia grade 3/4 in 100% of patients and 95% of cycles; febrile neutropenia in 34% of patients and 9% of cycles). Documented grade 3 infection was seen in one patient (2%) in one cycle, and no toxic death was reported. Severe acute or chronic nonhematologic adverse events were infrequent, and docetaxel-specific toxicities (such as fluid retention and nail changes) were mild, with only one patient being discontinued for fluid retention. Congestive heart failure was seen in two patients (4%). CONCLUSION: TAC is an active and manageable regimen that has been chosen as the basis of five randomized phase III trials, including two pivotal studies comparing TAC to fluorouracil plus doxorubicin and cyclophosphamide in the metastatic and adjuvant treatment of breast cancer.     

A study of fadrozole, a new aromatase inhibitor, in postmenopausal women with advanced metastatic breast cancer.

PURPOSE: The study investigated the therapeutic effects of fadrozole (CGS 16949A), a new aromatase inhibitor, in women who had received prior treatment for metastatic breast cancer. MATERIALS AND METHODS: Eighty postmenopausal women who had received prior treatment for metastatic breast cancer were randomized to receive fadrozole 1 mg/d or 4 mg/d per day orally. Seventy-eight patients were assessable for toxicity and response. RESULTS: Toxicity was limited to mild (grade 1) to moderate (grade 2) hot flashes in 28%, nausea and vomiting in 13%, fatigue in 8%, and mild loss of appetite in 5% of patients. No electrolyte or unanticipated hormonal changes occurred. The overall response was 23% (complete response, 10%; partial response, 13%). In addition, 45% of the patients had a no change status. There was no difference in response rate between the patients randomized to the two different doses of fadrozole. Only dominant site of metastases significantly affected response. The median time to treatment failure (TTF) was 4.4 months (4.7 months on 1 mg/d and 3.7 months on 4 mg/d). The median survival was 22.6 months (17.5 months on 1 mg/d; median survival has not been reached in patients on 4 mg/d). The response and survival in patients with estrogen receptor (ER)-positive and ER-unknown disease were not significantly different. CONCLUSIONS: Fadrozole has good therapeutic effect as a second-line treatment in postmenopausal women with metastatic breast cancer. In this study there was no significant difference in toxicity or response between 1 mg/d and 4 mg/d. Further trials comparing fadrozole to other hormone treatment are indicated.     

The results of diethylstilboestrol therapy for recurrent and metastatic carcinoma of the male breast.

A retrospective survey has been made of 58 patients with recurrent and advanced male breast cancer treated with oral diethylstilboestrol. Fifty-five patients were suitable for assessment. Fourteen patients had an objective response and 7 had a partial response giving a total response of 21/55 patients (38%). The median remission for the objective responders was 7 years. Three patients are alive and free of disease; one has now been in remission for 13 years. It is suggested that diethylstilboestrol is a useful treatment in patients with soft tissue disease (breast, chest wall and/or lymph nodes).     

VAMA salvage regimen (VP-16, ARA-C, MTX and L-asparaginase) in relapsed or resistant non-Hodgkin's lymphoma

A new salvage treatment protocol consisting of VP-16, cytosine arabinoside (Ara-C), methotrexate (MTX) and L-asparaginase, known as VAMA, was administered to twelve patients with relapsed or resistant non-Hodgkin's lymphoma. All twelve patients were in advanced stage with aggressive histologic type. Four of eight patients whose tumor cells had been immunologically determined, had T-cell phenotype. Three complete and five partial responses were obtained, for an overall response rate of 67%. It is of particular interest that all four patients with T-cell phenotype responded(CR; 3 cases, PR; 1 case), and a CR duration over 31 months has been achieved in a case of T-lymphoblastic lymphoma. Severe myelosuppression was the major toxic effect, but it was generally well-tolerated with supportive therapy. These results indicate that VAMA salvage regimen can play an important role in the treatment of relapsed or resistant non-Hodgkin's lymphoma.     

Etoposide,doxorubicin and cisplatin alternating with 5-fluorouracil,doxorubicin and high-dose methotrexate in patients with advanced adenocarcinoma of the stomach or the gastroesophageal junction

Both the etoposide, doxorubicin, cisplatin (EAP) and 5-fluorouracil, doxorubicin, high-dose methotrexate (FAMTX) schedules have been reported to be active in advanced gastric cancer. Since these regimens include non-cross resistant agents, a regimen that consists of EAP alternating with FAMTX may have an advantage over each regimen alone. We undertook a phase II trial to evaluate EAP/FAMTX in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction. Of the 56 patients treated, an objective response was observed in 34%, including complete response in 7%. Median response duration was 8 months and median survival for the entire group was 9 months. The main toxicity was myelosuppression. Hospitalization for granulocytopenic fever was required in 32% of patients and 34% required red blood cells (RBC) transfusion. Non-hematological toxicity was moderate. There were three drug-related deaths associated with granulocytopenic fever. We conclude that the alternating EAP/FAMTX regimen is associated with occasional lethal events and has no obvious advantage over either regimen alone.     

Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study.

PURPOSE: Surgical resection of liver-only metastases from colorectal cancer has undergone extensive evaluation and review. The use of neoadjuvant chemotherapy to improve the likelihood of resection in disease that is not optimally resectable has not been as well studied. PATIENTS AND METHODS: Patients with liver-only metastases from colorectal cancer deemed not optimally resectable by a surgeon with expertise in liver surgery received fluorouracil, leucovorin, and oxaliplatin (FOLFOX4). Patients were periodically reassessed for resectability. Surgical response was classified as completely resectable (S-CR), partially resectable (S-PR), or unresectable (S-UR). Study design specified the accrual of 39 patients, with two or more S-CRs considered evidence of promising activity with respect to increasing the S-CR rate. RESULTS: Forty-two of 44 patients were assessable for this analysis. Twenty-five patients (60%) had tumor reduction by serial imaging. Seventeen patients (40%) underwent surgery (S-CR, n = 14; S-PR, n = 1; and S-UR, n = 2) after a median of 6 months of chemotherapy. With a median postsurgical follow-up of 22 months (range, 13 to 32 months), 11 recurrences have occurred in the 15 S-CR and S-PR patients. Median survival time was 26 months. CONCLUSION: Our data suggest that FOLFOX4 has a high response rate (complete response, partial response, or reduction) in patients with liver-only metastases from colorectal cancer, allowing for successful resection of disease in a portion of patients initially not judged to be optimally resectable. However, a high recurrence rate after surgery was observed, which, in 73% of patients, involved the liver. Further trials are indicated based on the promising results observed in this trial.     

High-dose, continuous-infusion cyclophosphamide, cytarabine, vincristine, and prednisone for remission induction in refractory adult acute leukemia

Fifteen consecutive patients with refractory adult acute leukemia (RAAL) were treated with a combination of high-dose, continuous-infusion cyclophosphamide, cytarabine, vincristine, and prednisone (Hi-COAP). The initial nine patients received cyclophosphamide 350 mg/m2 as a 24-hour intravenous (IV) infusion over 5 days; cytarabine, 100 mg/m2 IV bolus every 12 hours for ten doses; vincristine, 2.0 mg IV bolus on day 1; and prednisone, 100 mg orally for 7 days. The last six patients had the cyclophosphamide infusion lengthened to 7 days, and the cytarabine increased to 14 doses. All patients were evaluable for toxicity and response. Seven patients (47%) obtained a complete remission and six patients (40%) a partial remission. Median duration of all remissions has been 7.0 months with a range of 1 to 32 months. Toxicity has been limited to primarily myelosuppression with no hemorrhagic cystitis, central nervous system (CNS), hepatic, or pulmonary toxicity noted. Gastrointestinal toxicity was mild, with no effect on nutritional status noted. Median duration of complete responders was 8.5 months. Thus, Hi-COAP demonstrates promising efficacy with minimal toxicity in RAAL and warrants further exploration in multiinstitutional trials.