Phase I/II Study to Evaluate the Efficacy and Safety of a Combination Chemotherapy

Inclusion Criteria:

* Histologically confirmed SCLC (adeno- and large cell, anaplastic carcinoma and broncho-alveolar-carcinoma). Patients with squamous-cell histology are eligible with extra thoracic or peripheral lung lesions only.
* Sputum cytology alone not acceptable evidence of cell type. Cytologic specimens obtained by brushing, washings, or needle aspiration of defined lesions will be acceptable. Mixed tumors will be categorized by the predominant cell type unless a small cell anaplastic elements are present, in which case the patient is ineligible.
* Stage III B because of pleural effusion or Stage IV disease
* Measurable disease.
* Age: 18 years or older
* No history of thrombotic, hemorrhagic, or coagulopathy disorders
* international normalized ratio (INR\<1.5) and a prothrombin time (PTT) no greater than normal limits of normal within 1 week prior to registration. NB: subjects with lung cancer placed on anticoagulant therapy for a thrombotic event are not eligible for this study.
* No gross hemoptysis (defined as bright red blood of ½ teaspoon or more)
* No central nervous system (CNS) or brain metastasis
* Laboratory Criteria (completed \<2 weeks before enrollment):

  * Hematologic: white blood cell (WBC) \> 3500/mm3 or absolute neutrophil count (ANC) \> 1500/mm3 and platelet count \> 100 000/ mm3;
  * Hepatic: Total bilirubin \< 1.5 mg/dl
  * Renal: Creatinine \< 1.5 mg/dl. or calculated
  * Creatinine clearance \> 45 ml/min (NB: Urine protein:creatinine ratio in exclusion criteria)
* Eastern Cooperative Oncology Group (ECOG) performance status \< 2
* Be free of active infection.
* Be available for active follow up.
* No prior chemotherapy for metastatic disease.
* Be disease free for \> 5 years if they had a prior second malignancy other than treated basal cell carcinoma or squamous cell skin cancer, or carcinoma in situ of the cervix.
* Female subject post-menopausal; surgically sterilized or willing to use an acceptable method of birth control for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

* CNS or brain metastasis
* Patient has = or greater Grade 2 peripheral neuropathy within 14 days before enrollment.
* Known previous sensitivity reactions with boron, or mannitol,
* Patients with known HIV positivity
* Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
* Blood pressure of \>150/100 mmHG
* History of myocardial infarction or stroke within 6 months
* Clinically significant peripheral vascular disease
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study.
* Minor surgical procedure such as fine needle aspirations or core biopsies within 7 days prior to day 0
* Urine protein: Creatinine ratio \> 1.0 at screening
* History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 0
* Serious, non-healing wound, ulcer, or bone fracture
* Lung carcinoma or any histology in close proximity to a major vessel or cavitation
* Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
* Patient has received other investigational drugs with 14 days before enrollment or is expected to participate in an experiment drug study during this study treatment.
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study.